15-90747136-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000057.4(BLM):c.-4-253G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0721 in 151,248 control chromosomes in the GnomAD database, including 718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.072 (718 hom., cov: 30)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.103

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-90747136-G-C is Benign according to our data. Variant chr15-90747136-G-C is described in ClinVar as [Benign]. Clinvar id is 1258326.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLM	NM_000057.4	c.-4-253G>C		intron_variant		ENST00000355112.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLM	ENST00000355112.8	c.-4-253G>C		intron_variant		1	NM_000057.4	P2

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10889 AN: 151134 Hom.: 719 Cov.: 30

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0489

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0839

Gnomad SAS AF: 0.0489

Gnomad FIN AF: 0.0456

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0228

Gnomad OTH AF: 0.0599

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

GnomAD4 genome AF: 0.0721 AC: 10903 AN: 151248 Hom.: 718 Cov.: 30 AF XY: 0.0725 AC XY: 5349 AN XY: 73820

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0491

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.0837

Gnomad4 SAS AF: 0.0481

Gnomad4 FIN AF: 0.0456

Gnomad4 NFE AF: 0.0228

Gnomad4 OTH AF: 0.0599

Alfa AF: 0.0169 Hom.: 11

Bravo AF: 0.0773

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.9
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2238335; hg19: chr15-91290366;