rs397815388

Positions:

• chr15-90815041-G-GGAA
• chr15-90815041-GGAA-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000057.4(BLM):​c.4077-59_4077-57dupAAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,533,884 control chromosomes in the GnomAD database, including 308,944 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31223 hom., cov: 0)
  • Exomes 𝑓: 0.63 (277721 hom.)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.130

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]

ENSG00000287061 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 15-90815041-G-GGAA is Benign according to our data. Variant chr15-90815041-G-GGAA is described in ClinVar as [Likely_benign]. Clinvar id is 210530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLM	NM_000057.4	c.4077-59_4077-57dupAAG		intron_variant		ENST00000355112.8	NP_000048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLM	ENST00000355112.8	c.4077-59_4077-57dupAAG		intron_variant		1	NM_000057.4	ENSP00000347232.3

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96752 AN: 151496 Hom.: 31190 Cov.: 0

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.631 AC: 871868 AN: 1382270 Hom.: 277721 AF XY: 0.629 AC XY: 435241 AN XY: 692044

Gnomad4 AFR exome AF: 0.627

Gnomad4 AMR exome AF: 0.769

Gnomad4 ASJ exome AF: 0.676

Gnomad4 EAS exome AF: 0.803

Gnomad4 SAS exome AF: 0.610

Gnomad4 FIN exome AF: 0.586

Gnomad4 NFE exome AF: 0.621

Gnomad4 OTH exome AF: 0.636

GnomAD4 genome AF: 0.639 AC: 96844 AN: 151614 Hom.: 31223 Cov.: 0 AF XY: 0.638 AC XY: 47283 AN XY: 74054

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.718

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.638

Alfa AF: 0.644 Hom.: 3360

Asia WGS AF: 0.700 AC: 2435 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 29, 2015

- -

Bloom syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10685387; hg19: chr15-91358271;