rs374616797

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_000057.4(BLM):c.2824-7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

BLM
NM_000057.4 splice_region, intron

Scores

Splicing: ADA: 0.00004036

Clinical Significance

Likely benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -2.05

Publications

0 publications found

Variant links:

Genes affected

BLM (HGNC:1058): (BLM RecQ like helicase) The Bloom syndrome is an autosomal recessive disorder characterized by growth deficiency, microcephaly and immunodeficiency among others. It is caused by homozygous or compound heterozygous mutation in the gene encoding DNA helicase RecQ protein on chromosome 15q26. This Bloom-associated helicase unwinds a variety of DNA substrates including Holliday junction, and is involved in several pathways contributing to the maintenance of genome stability. Identification of pathogenic Bloom variants is required for heterozygote testing in at-risk families. [provided by RefSeq, May 2020]

BLM Gene-Disease associations (from GenCC):

Bloom syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Orphanet, Genomics England PanelApp, ClinGen
osteosarcoma
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
breast cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

BLM links:

ENSG00000300894 (HGNC:):

ENSG00000300894 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 15-90790642-A-G is Benign according to our data. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-90790642-A-G is described in CliVar as Likely_benign. Clinvar id is 413293.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLM	NM_000057.4 link	c.2824-7A>G		splice_region_variant, intron_variant	Intron 14 of 21	ENST00000355112.8	NP_000048.1	P54132

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLM	ENST00000355112.8 link	c.2824-7A>G		splice_region_variant, intron_variant	Intron 14 of 21	1	NM_000057.4	ENSP00000347232.3		P54132

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461472

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727056

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111662

Other (OTH)

AF:

0.0000497

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Bloom syndrome

Uncertain:1Benign:1

Feb 03, 2019

Natera, Inc.

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 11, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.83

(source)

DANN

Benign

0.70

PhyloP100

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000040

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over