rs17273206

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000057.4(BLM):c.2308-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,363,766 control chromosomes in the GnomAD database, including 19,044 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2084 hom., cov: 32)

Exomes 𝑓: 0.16 ( 16960 hom. )

Consequence

BLM
NM_000057.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.357

Publications

15 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 15-90769083-G-A is Benign according to our data. Variant chr15-90769083-G-A is described in ClinVar as Benign. ClinVar VariationId is 254778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
BLM	NM_000057.4	MANE Select	c.2308-50G>A	intron	N/A	NP_000048.1	P54132
BLM	NM_001287246.2		c.2308-50G>A	intron	N/A	NP_001274175.1	P54132
BLM	NM_001287247.2		c.2308-50G>A	intron	N/A	NP_001274176.1	H0YNU5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BLM	ENST00000355112.8	TSL:1 MANE Select	c.2308-50G>A	intron	N/A	ENSP00000347232.3	P54132
BLM	ENST00000560509.5	TSL:1	c.2308-50G>A	intron	N/A	ENSP00000454158.1	H0YNU5
BLM	ENST00000559724.5	TSL:1	n.*1232-50G>A	intron	N/A	ENSP00000453359.1	H0YLV8

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24751

AN:

152058

Hom.:

2086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.0769

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.0884

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.152

GnomAD2 exomes

AF:

0.153

AC:

38439

AN:

251152

AF XY:

0.149

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.162

AC:

195945

AN:

1211590

Hom.:

16960

Cov.:

AF XY:

0.159

AC XY:

97925

AN XY:

615054

show subpopulations

African (AFR)

AF:

0.165

AC:

4657

AN:

28288

American (AMR)

AF:

0.116

AC:

5166

AN:

44380

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

3870

AN:

24592

East Asian (EAS)

AF:

0.232

AC:

8928

AN:

38546

South Asian (SAS)

AF:

0.0811

AC:

6582

AN:

81166

European-Finnish (FIN)

AF:

0.122

AC:

6491

AN:

53326

Middle Eastern (MID)

AF:

0.130

AC:

696

AN:

5356

European-Non Finnish (NFE)

AF:

0.171

AC:

151283

AN:

883760

Other (OTH)

AF:

0.159

AC:

8272

AN:

52176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

8994

17988

26983

35977

44971

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4680

9360

14040

18720

23400

<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:

0.163

AC:

24764

AN:

152176

Hom.:

2084

Cov.:

AF XY:

0.159

AC XY:

11799

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.167

AC:

6940

AN:

41516

American (AMR)

AF:

0.132

AC:

2025

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

559

AN:

3468

East Asian (EAS)

AF:

0.243

AC:

1257

AN:

5178

South Asian (SAS)

AF:

0.0881

AC:

425

AN:

4826

European-Finnish (FIN)

AF:

0.116

AC:

1225

AN:

10592

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.175

AC:

11894

AN:

67990

Other (OTH)

AF:

0.153

AC:

324

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1088

2175

3263

4350

5438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.173

Hom.:

575

Bravo

AF:

0.163

Asia WGS

AF:

0.159

AC:

555

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bloom syndrome (3)

not provided (2)

Hereditary cancer-predisposing syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.27

(source)

DANN

Benign

0.57

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over