rs732286

Positions:

• chr1-16017865-A-G
• chr1-16017865-A-T

Variant summary

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

The NM_014424.5(HSPB7):​c.99T>C​(p.Ala33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,613,290 control chromosomes in the GnomAD database, including 284,480 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 (28840 hom., cov: 35)
  • Exomes 𝑓: 0.59 (255640 hom.)
• Consequence: HSPB7 NM_014424.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

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=-0.63).
• BP7: Synonymous conserved (PhyloP=1.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPB7	NM_014424.5	c.99T>C	p.Ala33=	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.99T>C	p.Ala33=	synonymous_variant	1/3	1	NM_014424.5	ENSP00000310111	P3

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92890 AN: 152084 Hom.: 28818 Cov.: 35

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.623

GnomAD3 exomes AF: 0.576 AC: 142092 AN: 246776 Hom.: 41996 AF XY: 0.581 AC XY: 77750 AN XY: 133908

Gnomad AFR exome AF: 0.686

Gnomad AMR exome AF: 0.393

Gnomad ASJ exome AF: 0.511

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: 0.571

GnomAD4 exome AF: 0.590 AC: 861322 AN: 1461088 Hom.: 255640 Cov.: 52 AF XY: 0.590 AC XY: 428741 AN XY: 726814

Gnomad4 AFR exome AF: 0.701

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: 0.611 AC: 92952 AN: 152202 Hom.: 28840 Cov.: 35 AF XY: 0.605 AC XY: 45010 AN XY: 74402

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.621

Alfa AF: 0.600 Hom.: 12059

Bravo AF: 0.606

Asia WGS AF: 0.636 AC: 2211 AN: 3478

EpiCase AF: 0.589

EpiControl AF: 0.593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.90

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: rs732286; hg19: chr1-16344360; COSMIC: COSV58893088; COSMIC: COSV58893088;