rs7175811

Positions:

• chr15-90788316-G-A

Variant summary

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

The NM_000057.4(BLM):​c.2824-2333G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,852 control chromosomes in the GnomAD database, including 17,207 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 0.44 (17207 hom., cov: 31)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLM	NM_000057.4	c.2824-2333G>A		intron_variant		ENST00000355112.8	NP_000048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLM	ENST00000355112.8	c.2824-2333G>A		intron_variant		1	NM_000057.4	ENSP00000347232	P2

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67173 AN: 151734 Hom.: 17166 Cov.: 31

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.443 AC: 67274 AN: 151852 Hom.: 17207 Cov.: 31 AF XY: 0.436 AC XY: 32368 AN XY: 74194

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.397

Alfa AF: 0.344 Hom.: 18901

Bravo AF: 0.452

Asia WGS AF: 0.298 AC: 1037 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.63

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: rs7175811; hg19: chr15-91331546;