15-90780040-C-T

Position:

• chr15-90780040-C-T

Variant summary

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

The ENST00000355112.8(BLM):​c.2556-2782C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 150,080 control chromosomes in the GnomAD database, including 9,977 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 0.35 (9977 hom., cov: 30)
• Consequence: BLM ENST00000355112.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLM	NM_000057.4	c.2556-2782C>T		intron_variant		ENST00000355112.8	NP_000048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLM	ENST00000355112.8	c.2556-2782C>T		intron_variant		1	NM_000057.4	ENSP00000347232	P2

Frequencies

GnomAD3 genomes AF: 0.350 AC: 52491 AN: 150006 Hom.: 9956 Cov.: 30

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.350 AC: 52556 AN: 150080 Hom.: 9977 Cov.: 30 AF XY: 0.344 AC XY: 25134 AN XY: 73092

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.311

Alfa AF: 0.289 Hom.: 8636

Bravo AF: 0.348

Asia WGS AF: 0.212 AC: 739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.1
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: rs8037430; hg19: chr15-91323270;