15-90717714-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.-5+274G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 152,302 control chromosomes in the GnomAD database, including 1,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.092 (1960 hom., cov: 32)
• Consequence: BLM NM_000057.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29

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=-0.92).
• BP6: Variant 15-90717714-G-C is Benign according to our data. Variant chr15-90717714-G-C is described in ClinVar as [Benign]. Clinvar id is 1291120.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLM	NM_000057.4	c.-5+274G>C		intron_variant		ENST00000355112.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLM	ENST00000355112.8	c.-5+274G>C		intron_variant		1	NM_000057.4	P2

Frequencies

GnomAD3 genomes AF: 0.0916 AC: 13938 AN: 152184 Hom.: 1948 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0473

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0385

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00342

Gnomad OTH AF: 0.0716

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

GnomAD4 genome AF: 0.0918 AC: 13985 AN: 152302 Hom.: 1960 Cov.: 32 AF XY: 0.0911 AC XY: 6782 AN XY: 74482

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.0383

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.0468

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.0385

Gnomad4 NFE AF: 0.00343

Gnomad4 OTH AF: 0.0709

Alfa AF: 0.0554 Hom.: 130

Bravo AF: 0.103

Asia WGS AF: 0.0510 AC: 175 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	-0.92
Cadd	Benign	0.93
Dann	Benign	0.60

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: rs7163120; hg19: chr15-91260945;