Variant 15-90751667-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000057.4(BLM):c.800-120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 797,304 control chromosomes in the GnomAD database, including 14,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3281 hom., cov: 32)

Exomes 𝑓: 0.18 ( 11259 hom. )

Consequence

BLM
NM_000057.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.538

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 15-90751667-T-C is Benign according to our data. Variant chr15-90751667-T-C is described in ClinVar as [Benign]. Clinvar id is 1177546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLM	NM_000057.4 link	c.800-120T>C		intron_variant		ENST00000355112.8	NP_000048.1	P54132

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLM	ENST00000355112.8 link	c.800-120T>C		intron_variant		1	NM_000057.4	ENSP00000347232.3		P54132

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30548

AN:

152076

Hom.:

3280

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.174

GnomAD4 exome

AF:

0.180

AC:

115862

AN:

645110

Hom.:

11259

AF XY:

0.176

AC XY:

60168

AN XY:

342766

show subpopulations

Gnomad4 AFR exome

AF:

0.277

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.153

Gnomad4 EAS exome

AF:

0.234

Gnomad4 SAS exome

AF:

0.0952

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.192

Gnomad4 OTH exome

AF:

0.174

GnomAD4 genome

AF:

0.201

AC:

30568

AN:

152194

Hom.:

3281

Cov.:

AF XY:

0.197

AC XY:

14639

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.271

Gnomad4 AMR

AF:

0.151

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.140

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.175

Alfa

AF:

0.0901

Hom.:

157

Bravo

AF:

0.203

Asia WGS

AF:

0.182

AC:

632

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Bloom syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.5

DANN

Benign

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over