rs1739840

chr1-16015742-A-Gchr1-16015742-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.351T>C(p.Thr117=) 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 1,588,860 control chromosomes in the GnomAD database, including 281,129 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 (29272 hom., cov: 33)
  • Exomes 𝑓: 0.59 (251857 hom.)
• Consequence: HSPB7 NM_014424.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.44

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=-1.0).
• BP7: Synonymous conserved (PhyloP=-8.44 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPB7	NM_014424.5	c.351T>C	p.Thr117=	synonymous_variant	3/3	ENST00000311890.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPB7	ENST00000311890.14	c.351T>C	p.Thr117=	synonymous_variant	3/3	1	NM_014424.5	P3

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93453 AN: 151940 Hom.: 29251 Cov.: 33

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.625

GnomAD3 exomes AF: 0.580 AC: 138499 AN: 238962 Hom.: 41186 AF XY: 0.584 AC XY: 75440 AN XY: 129180

Gnomad AFR exome AF: 0.702

Gnomad AMR exome AF: 0.393

Gnomad ASJ exome AF: 0.517

Gnomad EAS exome AF: 0.753

Gnomad SAS exome AF: 0.594

Gnomad FIN exome AF: 0.568

Gnomad NFE exome AF: 0.594

Gnomad OTH exome AF: 0.572

GnomAD4 exome AF: 0.590 AC: 847795 AN: 1436802 Hom.: 251857 Cov.: 51 AF XY: 0.590 AC XY: 419675 AN XY: 710856

Gnomad4 AFR exome AF: 0.715

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.518

Gnomad4 EAS exome AF: 0.729

Gnomad4 SAS exome AF: 0.587

Gnomad4 FIN exome AF: 0.564

Gnomad4 NFE exome AF: 0.591

Gnomad4 OTH exome AF: 0.605

GnomAD4 genome AF: 0.615 AC: 93514 AN: 152058 Hom.: 29272 Cov.: 33 AF XY: 0.610 AC XY: 45299 AN XY: 74302

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.623

Alfa AF: 0.594 Hom.: 6957

Bravo AF: 0.611

Asia WGS AF: 0.638 AC: 2218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.0050
Dann	Benign	0.63

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: rs1739840; hg19: chr1-16342237;