rs945416

Positions:

• chr1-16017907-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014424.5(HSPB7):​c.57C>T​(p.Ser19=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,613,376 control chromosomes in the GnomAD database, including 284,168 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (28782 hom., cov: 35)
  • Exomes 𝑓: 0.59 (255386 hom.)
• Consequence: HSPB7 NM_014424.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-1.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPB7	NM_014424.5	c.57C>T	p.Ser19=	synonymous_variant	1/3	ENST00000311890.14	NP_055239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPB7	ENST00000311890.14	c.57C>T	p.Ser19=	synonymous_variant	1/3	1	NM_014424.5	ENSP00000310111	P3

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92772 AN: 152084 Hom.: 28761 Cov.: 35

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.622

GnomAD3 exomes AF: 0.576 AC: 142795 AN: 248018 Hom.: 42219 AF XY: 0.581 AC XY: 78047 AN XY: 134424

Gnomad AFR exome AF: 0.686

Gnomad AMR exome AF: 0.392

Gnomad ASJ exome AF: 0.510

Gnomad EAS exome AF: 0.752

Gnomad SAS exome AF: 0.590

Gnomad FIN exome AF: 0.566

Gnomad NFE exome AF: 0.592

Gnomad OTH exome AF: 0.570

GnomAD4 exome AF: 0.589 AC: 860908 AN: 1461174 Hom.: 255386 Cov.: 50 AF XY: 0.590 AC XY: 428533 AN XY: 726860

Gnomad4 AFR exome AF: 0.699

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.728

Gnomad4 SAS exome AF: 0.586

Gnomad4 FIN exome AF: 0.565

Gnomad4 NFE exome AF: 0.591

Gnomad4 OTH exome AF: 0.603

GnomAD4 genome AF: 0.610 AC: 92833 AN: 152202 Hom.: 28782 Cov.: 35 AF XY: 0.604 AC XY: 44954 AN XY: 74400

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.621

Alfa AF: 0.588 Hom.: 19286

Bravo AF: 0.605

Asia WGS AF: 0.638 AC: 2219 AN: 3478

EpiCase AF: 0.588

EpiControl AF: 0.593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.3
DANN	Benign	0.92

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: rs945416; hg19: chr1-16344402; COSMIC: COSV58893094; COSMIC: COSV58893094;