rs945417

chr1-16018130-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349682.2(HSPB7):c.337-278G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,546,386 control chromosomes in the GnomAD database, including 251,782 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 0.60 (28043 hom., cov: 33)
  • Exomes 𝑓: 0.56 (223739 hom.)
• Consequence: HSPB7 NM_001349682.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• 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	UniProt
HSPB7	NM_001349682.2	c.337-278G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPB7	ENST00000375718.4	c.337-278G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.599 AC: 91041 AN: 151978 Hom.: 28017 Cov.: 33

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.608

GnomAD3 exomes AF: 0.546 AC: 82419 AN: 151064 Hom.: 23276 AF XY: 0.551 AC XY: 44828 AN XY: 81412

Gnomad AFR exome AF: 0.722

Gnomad AMR exome AF: 0.395

Gnomad ASJ exome AF: 0.459

Gnomad EAS exome AF: 0.758

Gnomad SAS exome AF: 0.558

Gnomad FIN exome AF: 0.524

Gnomad NFE exome AF: 0.562

Gnomad OTH exome AF: 0.545

GnomAD4 exome AF: 0.564 AC: 786154 AN: 1394290 Hom.: 223739 Cov.: 57 AF XY: 0.564 AC XY: 387679 AN XY: 687786

Gnomad4 AFR exome AF: 0.731

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.456

Gnomad4 EAS exome AF: 0.730

Gnomad4 SAS exome AF: 0.558

Gnomad4 FIN exome AF: 0.528

Gnomad4 NFE exome AF: 0.562

Gnomad4 OTH exome AF: 0.579

GnomAD4 genome AF: 0.599 AC: 91107 AN: 152096 Hom.: 28043 Cov.: 33 AF XY: 0.592 AC XY: 44046 AN XY: 74360

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.606

Alfa AF: 0.562 Hom.: 7863

Bravo AF: 0.598

Asia WGS AF: 0.631 AC: 2195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	17
Dann	Benign	0.93

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: rs945417; hg19: chr1-16344625; COSMIC: COSV58890268; COSMIC: COSV58890268;