rs1058872

Positions:

chr7-76304184-C-T

Variant summary

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

The NM_001540.5(HSPB1):c.*11C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,604,494 control chromosomes in the GnomAD database, including 309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 100 hom., cov: 32)

Exomes 𝑓: 0.012 ( 209 hom. )

Consequence

HSPB1
NM_001540.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.13

Variant links:

Genes affected

HSPB1 (HGNC:5246): (heat shock protein family B (small) member 1) This gene encodes a member of the small heat shock protein (HSP20) family of proteins. In response to environmental stress, the encoded protein translocates from the cytoplasm to the nucleus and functions as a molecular chaperone that promotes the correct folding of other proteins. This protein plays an important role in the differentiation of a wide variety of cell types. Expression of this gene is correlated with poor clinical outcome in multiple human cancers, and the encoded protein may promote cancer cell proliferation and metastasis, while protecting cancer cells from apoptosis. Mutations in this gene have been identified in human patients with Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. [provided by RefSeq, Aug 2017]

HSPB1 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=-0.73).

BP6

Variant 7-76304184-C-T is Benign according to our data. Variant chr7-76304184-C-T is described in ClinVar as [Benign]. Clinvar id is 258164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-76304184-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPB1	NM_001540.5 linkuse as main transcript	c.*11C>T		3_prime_UTR_variant	3/3	ENST00000248553.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPB1	ENST00000248553.7 linkuse as main transcript	c.*11C>T		3_prime_UTR_variant	3/3	1	NM_001540.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0252

AC:

3833

AN:

152130

Hom.:

102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0594

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0220

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0232

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.0292

GnomAD3 exomes

AF:

0.0149

AC:

3388

AN:

226686

Hom.:

AF XY:

0.0143

AC XY:

1776

AN XY:

124072

show subpopulations

Gnomad AFR exome

AF:

0.0667

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.0394

Gnomad EAS exome

AF:

0.000120

Gnomad SAS exome

AF:

0.0207

Gnomad FIN exome

AF:

0.000758

Gnomad NFE exome

AF:

0.00967

Gnomad OTH exome

AF:

0.0182

GnomAD4 exome

AF:

0.0117

AC:

17011

AN:

1452246

Hom.:

209

Cov.:

AF XY:

0.0118

AC XY:

8532

AN XY:

721830

show subpopulations

Gnomad4 AFR exome

AF:

0.0590

Gnomad4 AMR exome

AF:

0.0140

Gnomad4 ASJ exome

AF:

0.0407

Gnomad4 EAS exome

AF:

0.0000513

Gnomad4 SAS exome

AF:

0.0210

Gnomad4 FIN exome

AF:

0.000712

Gnomad4 NFE exome

AF:

0.00926

Gnomad4 OTH exome

AF:

0.0177

GnomAD4 genome

AF:

0.0251

AC:

3828

AN:

152248

Hom.:

100

Cov.:

AF XY:

0.0246

AC XY:

1830

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0592

Gnomad4 AMR

AF:

0.0219

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0230

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0216

Hom.:

Bravo

AF:

0.0281

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Charcot-Marie-Tooth disease axonal type 2F

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Neuronopathy, distal hereditary motor, type 2B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.0

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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