rs17181698

chr15-90765498-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000057.4(BLM):c.2193+84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0699 in 1,121,778 control chromosomes in the GnomAD database, including 3,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.069 (423 hom., cov: 32)
  • Exomes 𝑓: 0.070 (2657 hom.)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0840

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-90765498-C-T is Benign according to our data. Variant chr15-90765498-C-T is described in ClinVar as [Benign]. Clinvar id is 1235895.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLM	NM_000057.4	c.2193+84C>T		intron_variant		ENST00000355112.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLM	ENST00000355112.8	c.2193+84C>T		intron_variant		1	NM_000057.4	P2

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 10478 AN: 152070 Hom.: 420 Cov.: 32

Gnomad AFR AF: 0.0615

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0770

Gnomad OTH AF: 0.0677

GnomAD4 exome AF: 0.0701 AC: 67945 AN: 969590 Hom.: 2657 AF XY: 0.0693 AC XY: 34665 AN XY: 500246

Gnomad4 AFR exome AF: 0.0616

Gnomad4 AMR exome AF: 0.0477

Gnomad4 ASJ exome AF: 0.0471

Gnomad4 EAS exome AF: 0.000557

Gnomad4 SAS exome AF: 0.0445

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0773

Gnomad4 OTH exome AF: 0.0679

GnomAD4 genome AF: 0.0690 AC: 10494 AN: 152188 Hom.: 423 Cov.: 32 AF XY: 0.0687 AC XY: 5107 AN XY: 74390

Gnomad4 AFR AF: 0.0618

Gnomad4 AMR AF: 0.0632

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0483

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0770

Gnomad4 OTH AF: 0.0670

Alfa AF: 0.0708 Hom.: 49

Bravo AF: 0.0655

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.0
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs17181698; hg19: chr15-91308728;