chr15-90769593-T-C

Position:

chr15-90769593-T-C

Variant summary

Our verdict is Benign. Variant got -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:12

Conservation

PhyloP100: 1.04

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 links:

BLM (HGNC:):

BLM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 92392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-90769593-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLM	NM_000057.4 linkuse as main transcript	c.2555+7T>C		splice_region_variant, intron_variant		ENST00000355112.8	NP_000048.1	P54132

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLM	ENST00000355112.8 linkuse as main transcript	c.2555+7T>C		splice_region_variant, intron_variant		1	NM_000057.4	ENSP00000347232.3		P54132

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

GnomAD3 exomes

AF:

0.280

AC:

69977

AN:

250054

Hom.:

10864

AF XY:

0.269

AC XY:

36409

AN XY:

135158

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 SAS exome

AF:

0.179

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

Gnomad4 AFR exome

AF:

0.605

Gnomad4 AMR exome

AF:

0.238

Gnomad4 ASJ exome

AF:

0.233

Gnomad4 EAS exome

AF:

0.313

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.275

Gnomad4 NFE exome

AF:

0.281

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.361

AC:

54798

AN:

151848

Hom.:

11405

Cov.:

AF XY:

0.354

AC XY:

26249

AN XY:

74160

show subpopulations

Gnomad4 AFR

AF:

0.582

Gnomad4 AMR

AF:

0.274

Gnomad4 ASJ

AF:

0.226

Gnomad4 EAS

AF:

0.316

Gnomad4 SAS

AF:

0.192

Gnomad4 FIN

AF:

0.273

Gnomad4 NFE

AF:

0.286

Gnomad4 OTH

AF:

0.320

Alfa

AF:

0.306

Hom.:

7206

Bravo

AF:

0.370

Asia WGS

AF:

0.274

AC:

952

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bloom syndrome

Benign:6

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Mar 28, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 06, 2023	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 29, 2013	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over