15-90769593-T-C

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.2555+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,612,356 control chromosomes in the GnomAD database, including 72,224 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11405 hom., cov: 31)

Exomes 𝑓: 0.28 ( 60819 hom. )

Consequence

BLM
NM_000057.4 splice_region, intron

Scores

Splicing: ADA: 0.001295

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 1.04

Publications

29 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=-0.54).

BP6

Variant 15-90769593-T-C is Benign according to our data. Variant chr15-90769593-T-C is described in ClinVar as Benign. ClinVar VariationId is 92392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 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.2555+7T>C	splice_region intron	N/A	NP_000048.1	P54132
BLM	NM_001287246.2		c.2555+7T>C	splice_region intron	N/A	NP_001274175.1	P54132
BLM	NM_001287247.2		c.2555+7T>C	splice_region 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.2555+7T>C	splice_region intron	N/A	ENSP00000347232.3	P54132
BLM	ENST00000560509.5	TSL:1	c.2555+7T>C	splice_region intron	N/A	ENSP00000454158.1	H0YNU5
BLM	ENST00000559724.5	TSL:1	n.*1479+7T>C	splice_region intron	N/A	ENSP00000453359.1	H0YLV8

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54735

AN:

151730

Hom.:

11388

Cov.:

show subpopulations

Gnomad AFR

AF:

0.582

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.319

GnomAD2 exomes

AF:

0.280

AC:

69977

AN:

250054

AF XY:

0.269

show subpopulations

Gnomad AFR exome

AF:

0.597

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.316

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.277

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.281

AC:

410940

AN:

1460508

Hom.:

60819

Cov.:

AF XY:

0.277

AC XY:

201321

AN XY:

726542

show subpopulations

African (AFR)

AF:

0.605

AC:

20218

AN:

33444

American (AMR)

AF:

0.238

AC:

10621

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

6087

AN:

26128

East Asian (EAS)

AF:

0.313

AC:

12411

AN:

39670

South Asian (SAS)

AF:

0.182

AC:

15685

AN:

86222

European-Finnish (FIN)

AF:

0.275

AC:

14674

AN:

53394

Middle Eastern (MID)

AF:

0.201

AC:

1131

AN:

5636

European-Non Finnish (NFE)

AF:

0.281

AC:

312762

AN:

1111086

Other (OTH)

AF:

0.288

AC:

17351

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

15506

31013

46519

62026

77532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10440

20880

31320

41760

52200

<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:

0.361

AC:

54798

AN:

151848

Hom.:

11405

Cov.:

AF XY:

0.354

AC XY:

26249

AN XY:

74160

show subpopulations

African (AFR)

AF:

0.582

AC:

24085

AN:

41390

American (AMR)

AF:

0.274

AC:

4187

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

784

AN:

3464

East Asian (EAS)

AF:

0.316

AC:

1631

AN:

5156

South Asian (SAS)

AF:

0.192

AC:

923

AN:

4808

European-Finnish (FIN)

AF:

0.273

AC:

2873

AN:

10516

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.286

AC:

19399

AN:

67932

Other (OTH)

AF:

0.320

AC:

674

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1603

3206

4808

6411

8014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.308

Hom.:

9045

Bravo

AF:

0.370

Asia WGS

AF:

0.274

AC:

952

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bloom syndrome (6)

not specified (4)

not provided (2)

Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0013

dbscSNV1_RF

Benign

0.0020

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