rs2270132

Positions:

• chr15-90808638-A-C
• chr15-90808638-A-T

Variant summary

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

The NM_000057.4(BLM):​c.3752-499A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 199,500 control chromosomes in the GnomAD database, including 15,646 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 (11246 hom., cov: 33)
  • Exomes 𝑓: 0.41 (4400 hom.)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLM	NM_000057.4	c.3752-499A>C		intron_variant		ENST00000355112.8	NP_000048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLM	ENST00000355112.8	c.3752-499A>C		intron_variant		1	NM_000057.4	ENSP00000347232	P2

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54742 AN: 152088 Hom.: 11250 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.411 AC: 19432 AN: 47294 Hom.: 4400 AF XY: 0.412 AC XY: 10098 AN XY: 24492

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.550

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.549

Gnomad4 SAS exome AF: 0.480

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.360 AC: 54765 AN: 152206 Hom.: 11246 Cov.: 33 AF XY: 0.365 AC XY: 27147 AN XY: 74412

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.393

Alfa AF: 0.384 Hom.: 5828

Bravo AF: 0.362

Asia WGS AF: 0.472 AC: 1642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.013
DANN	Benign	0.70

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: rs2270132; hg19: chr15-91351868;