chr1-16017815-T-G

Position:

• chr1-16017815-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.64

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]

ACMG classification

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	UniProt
HSPB7	NM_014424.5	c.149A>C	p.Asp50Ala	missense_variant	1/3	ENST00000311890.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPB7	ENST00000311890.14	c.149A>C	p.Asp50Ala	missense_variant	1/3	1	NM_014424.5	P3

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152090 Hom.: 0 Cov.: 34

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: 5 AN: 1461166 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726858

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: 5 AN: 152090 Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4 AN XY: 74288

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	.;T;.;T;.;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.010
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.80	T;T;T;T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Uncertain	0.14	D
MutationAssessor	Benign	0.97	.;L;.;.;L;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.65	T
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	D
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

Other links and lift over

dbSNP: rs892849133; hg19: chr1-16344310;