rs6496724

chr15-90746500-A-C

Variant summary

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

The NM_000057.4(BLM):c.-4-889A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,068 control chromosomes in the GnomAD database, including 11,443 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 0.36 (11443 hom., cov: 31)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLM	NM_000057.4	c.-4-889A>C		intron_variant		ENST00000355112.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLM	ENST00000355112.8	c.-4-889A>C		intron_variant		1	NM_000057.4	P2

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54166 AN: 151948 Hom.: 11429 Cov.: 31

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.357 AC: 54220 AN: 152068 Hom.: 11443 Cov.: 31 AF XY: 0.352 AC XY: 26156 AN XY: 74338

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.324

Alfa AF: 0.334 Hom.: 1570

Bravo AF: 0.366

Asia WGS AF: 0.302 AC: 1051 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.0
Dann	Benign	0.78

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: rs6496724; hg19: chr15-91289730;