Variant chr1-16017815-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014424.5(HSPB7):c.149A>C(p.Asp50Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

HSPB7
NM_014424.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.64

Variant links:

Genes affected

HSPB7 (HGNC:5249): (heat shock protein family B (small) member 7) This gene encodes a small heat shock family B member that can heterodimerize with similar heat shock proteins. Defects in this gene are associated with advanced heart failure. In addition, the encoded protein may be a tumor suppressor in the p53 pathway, with defects in this gene being associated with renal cell carcinoma. [provided by RefSeq, Mar 2017]

HSPB7 links:

HSPB7 (HGNC:):

HSPB7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31865364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPB7	NM_014424.5 linkuse as main transcript	c.149A>C	p.Asp50Ala	missense_variant	1/3	ENST00000311890.14	NP_055239.1	Q9UBY9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPB7	ENST00000311890.14 linkuse as main transcript	c.149A>C	p.Asp50Ala	missense_variant	1/3	1	NM_014424.5	ENSP00000310111.9		Q9UBY9-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461166

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.000106

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2024

The c.149A>C (p.D50A) alteration is located in exon 1 (coding exon 1) of the HSPB7 gene. This alteration results from a A to C substitution at nucleotide position 149, causing the aspartic acid (D) at amino acid position 50 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

.;T;.;T;.;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.010

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.80

T;T;T;T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.32

T;T;T;T;T;T

MetaSVM

Uncertain

0.14

MutationAssessor

Benign

0.97

.;L;.;.;L;.

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.9

N;N;N;N;D;N

REVEL

Benign

0.27

Sift

Uncertain

0.029

D;D;D;D;T;D

Sift4G

Uncertain

0.033

D;D;D;D;D;T

Polyphen

0.0050, 0.82

.;B;P;.;.;.

Vest4

0.34

MutPred

0.22

.;.;Loss of stability (P = 0.0461);.;.;.;

MVP

0.98

MPC

0.46

ClinPred

0.85

GERP RS

4.6

Varity_R

0.13

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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