15-90813274-T-C

Position:

• chr15-90813274-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000057.4(BLM):​c.4077-1828T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,206 control chromosomes in the GnomAD database, including 8,819 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (8819 hom., cov: 33)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLM	NM_000057.4	c.4077-1828T>C		intron_variant		ENST00000355112.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLM	ENST00000355112.8	c.4077-1828T>C		intron_variant		1	NM_000057.4	P2
	ENST00000656405.1	n.590-542A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48654 AN: 152088 Hom.: 8821 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.331

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.320 AC: 48676 AN: 152206 Hom.: 8819 Cov.: 33 AF XY: 0.326 AC XY: 24261 AN XY: 74422

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.332

Alfa AF: 0.356 Hom.: 13428

Bravo AF: 0.323

Asia WGS AF: 0.450 AC: 1563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.71

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: rs401549; hg19: chr15-91356504;