15-90797765-A-G

Position:

• chr15-90797765-A-G

Variant summary

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

The NM_000057.4(BLM):​c.3211-425A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,010 control chromosomes in the GnomAD database, including 11,373 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 (11373 hom., cov: 31)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711

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]

BLM (HGNC:):

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 = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLM	NM_000057.4	c.3211-425A>G		intron_variant		ENST00000355112.8	NP_000048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLM	ENST00000355112.8	c.3211-425A>G		intron_variant		1	NM_000057.4	ENSP00000347232.3

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54900 AN: 151892 Hom.: 11345 Cov.: 31

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.362 AC: 54983 AN: 152010 Hom.: 11373 Cov.: 31 AF XY: 0.354 AC XY: 26296 AN XY: 74316

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.336

Alfa AF: 0.357 Hom.: 1360

Bravo AF: 0.374

Asia WGS AF: 0.252 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.20

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: rs2380165; hg19: chr15-91340995;