rs369629509

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong

The NM_000057.4(BLM):c.3062A>G(p.Asn1021Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000199 in 1,606,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1021D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

BLM
NM_000057.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 5.97

Publications

2 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, Genomics England PanelApp, ClinGen, Laboratory for Molecular Medicine
osteosarcoma
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
colorectal cancer
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20756114).

BP6

Variant 15-90794209-A-G is Benign according to our data. Variant chr15-90794209-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 454126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000057.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BLM	NM_000057.4	MANE Select	c.3062A>G	p.Asn1021Ser	missense	Exon 16 of 22	NP_000048.1	P54132
BLM	NM_001287246.2		c.3062A>G	p.Asn1021Ser	missense	Exon 17 of 23	NP_001274175.1	P54132
BLM	NM_001287247.2		c.3062A>G	p.Asn1021Ser	missense	Exon 16 of 20	NP_001274176.1	H0YNU5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BLM	ENST00000355112.8	TSL:1 MANE Select	c.3062A>G	p.Asn1021Ser	missense	Exon 16 of 22	ENSP00000347232.3	P54132
BLM	ENST00000560509.5	TSL:1	c.3062A>G	p.Asn1021Ser	missense	Exon 16 of 20	ENSP00000454158.1	H0YNU5
BLM	ENST00000559724.5	TSL:1	n.*1986A>G		non_coding_transcript_exon	Exon 16 of 22	ENSP00000453359.1	H0YLV8

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000242

AC:

AN:

248262

AF XY:

0.0000373

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000884

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1453874

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

723188

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33326

American (AMR)

AF:

0.0000679

AC:

AN:

44180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25986

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39282

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53140

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00000632

AC:

AN:

1107422

Other (OTH)

AF:

0.0000500

AC:

AN:

60016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.0000591

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.0000718

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bloom syndrome (2)

Hereditary cancer-predisposing syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Benign

-0.016

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.029

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.43

PhyloP100

6.0

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.33

Sift

Benign

0.059

Sift4G

Uncertain

0.026

Polyphen

0.16

Vest4

0.16

MVP

0.84

MPC

0.12

ClinPred

0.19

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.17

gMVP

0.63

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over