chr15-90769083-G-A

Variant names:

• chr15-90769083-G-A
• rs17273206
• NM_000057.4:c.2308-50G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.357
• Publications: 15 publications found

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: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Orphanet, Genomics England PanelApp, ClinGen
• osteosarcoma

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• breast cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLM	NM_000057.4	MANE Select	c.2308-50G>A		intron	N/A	NP_000048.1
	BLM	NM_001287246.2		c.2308-50G>A		intron	N/A	NP_001274175.1
	BLM	NM_001287247.2		c.2308-50G>A		intron	N/A	NP_001274176.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24751 AN: 152058 Hom.: 2086 Cov.: 32

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

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.: 18 AF XY: 0.159 AC XY: 97925 AN XY: 615054

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

GnomAD4 genome AF: 0.163 AC: 24764 AN: 152176 Hom.: 2084 Cov.: 32 AF XY: 0.159 AC XY: 11799 AN XY: 74392

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: 45 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11894 AN: 67990

Other (OTH) AF: 0.153 AC: 324 AN: 2116

Alfa AF: 0.173 Hom.: 575

Bravo AF: 0.163

Asia WGS AF: 0.159 AC: 555 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Bloom syndrome Benign:3

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Apr 06, 2018

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Hereditary cancer-predisposing syndrome Benign:1

Jul 10, 2025

GeneKor MSA

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.57
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17273206; hg19: chr15-91312313; COSMIC: COSV61924244;