rs17273206

Positions:

• chr15-90769083-G-A

Variant summary

Our verdict is Benign. Variant got -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:5
• Conservation: PhyloP100: -0.357

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLM	NM_000057.4	c.2308-50G>A		intron_variant		ENST00000355112.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLM	ENST00000355112.8	c.2308-50G>A		intron_variant		1	NM_000057.4	P2

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

GnomAD3 exomes AF: 0.153 AC: 38439 AN: 251152 Hom.: 3193 AF XY: 0.149 AC XY: 20293 AN XY: 135750

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 SAS exome AF: 0.0789

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

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.232

Gnomad4 SAS exome AF: 0.0811

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.159

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

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.0881

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.153

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Bloom syndrome Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 06, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.57

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

LitVar

Other links and lift over

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