rs17273842

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.3358+32T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,603,142 control chromosomes in the GnomAD database, including 23,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2153 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21815 hom. )

Consequence

BLM
NM_000057.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.297

Publications

11 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 15-90798369-T-G is Benign according to our data. Variant chr15-90798369-T-G is described in ClinVar as Benign. ClinVar VariationId is 254780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 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.3358+32T>G	intron	N/A	NP_000048.1	P54132
BLM	NM_001287246.2		c.3358+32T>G	intron	N/A	NP_001274175.1	P54132
BLM	NM_001287247.2		c.3358+32T>G	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.3358+32T>G	intron	N/A	ENSP00000347232.3	P54132
BLM	ENST00000560509.5	TSL:1	c.3358+32T>G	intron	N/A	ENSP00000454158.1	H0YNU5
BLM	ENST00000559724.5	TSL:1	n.*2282+32T>G	intron	N/A	ENSP00000453359.1	H0YLV8

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25028

AN:

152114

Hom.:

2152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.0921

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.154

GnomAD2 exomes

AF:

0.155

AC:

38443

AN:

248226

AF XY:

0.153

show subpopulations

Gnomad AFR exome

AF:

0.163

Gnomad AMR exome

AF:

0.0902

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.187

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.170

AC:

247220

AN:

1450910

Hom.:

21815

Cov.:

AF XY:

0.168

AC XY:

121456

AN XY:

721856

show subpopulations

African (AFR)

AF:

0.159

AC:

5305

AN:

33276

American (AMR)

AF:

0.0949

AC:

4199

AN:

44266

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

4290

AN:

25998

East Asian (EAS)

AF:

0.176

AC:

6953

AN:

39418

South Asian (SAS)

AF:

0.0885

AC:

7544

AN:

85238

European-Finnish (FIN)

AF:

0.146

AC:

7666

AN:

52442

Middle Eastern (MID)

AF:

0.142

AC:

811

AN:

5716

European-Non Finnish (NFE)

AF:

0.182

AC:

200508

AN:

1104514

Other (OTH)

AF:

0.166

AC:

9944

AN:

60042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

8978

17956

26933

35911

44889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6824

13648

20472

27296

34120

<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:

0.165

AC:

25051

AN:

152232

Hom.:

2153

Cov.:

AF XY:

0.160

AC XY:

11893

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.159

AC:

6610

AN:

41526

American (AMR)

AF:

0.114

AC:

1746

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

595

AN:

3468

East Asian (EAS)

AF:

0.178

AC:

925

AN:

5186

South Asian (SAS)

AF:

0.0930

AC:

449

AN:

4828

European-Finnish (FIN)

AF:

0.145

AC:

1541

AN:

10608

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.187

AC:

12726

AN:

68000

Other (OTH)

AF:

0.154

AC:

325

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1079

2158

3236

4315

5394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

268

536

804

1072

1340

<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:

0.182

Hom.:

888

Bravo

AF:

0.162

Asia WGS

AF:

0.138

AC:

479

AN:

3472

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

-0.86

CADD

Benign

0.90

(source)

DANN

Benign

0.65

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism (auto)

(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