chr1-16017999-G-A

Position:

• chr1-16017999-G-A

Variant summary

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

The NM_014424.5(HSPB7):​c.-36C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,611,614 control chromosomes in the GnomAD database, including 284,164 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 (28775 hom., cov: 35)
  • Exomes 𝑓: 0.59 (255389 hom.)
• Consequence: HSPB7 NM_014424.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.824

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=-0.62).
• 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	UniProt
HSPB7	NM_014424.5	c.-36C>T		5_prime_UTR_variant	1/3	ENST00000311890.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPB7	ENST00000311890.14	c.-36C>T		5_prime_UTR_variant	1/3	1	NM_014424.5	P3

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92762 AN: 152042 Hom.: 28754 Cov.: 35

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.511

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: 0.622

GnomAD3 exomes AF: 0.576 AC: 139812 AN: 242582 Hom.: 41324 AF XY: 0.581 AC XY: 77037 AN XY: 132502

Gnomad AFR exome AF: 0.687

Gnomad AMR exome AF: 0.393

Gnomad ASJ exome AF: 0.512

Gnomad EAS exome AF: 0.753

Gnomad SAS exome AF: 0.591

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.593

Gnomad OTH exome AF: 0.571

GnomAD4 exome AF: 0.590 AC: 860448 AN: 1459454 Hom.: 255389 Cov.: 59 AF XY: 0.590 AC XY: 428290 AN XY: 725940

Gnomad4 AFR exome AF: 0.699

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.729

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: 92823 AN: 152160 Hom.: 28775 Cov.: 35 AF XY: 0.605 AC XY: 44958 AN XY: 74372

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.511

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: 0.574 Hom.: 9418

Bravo AF: 0.604

Asia WGS AF: 0.638 AC: 2218 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.85

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: rs1572381; hg19: chr1-16344494; COSMIC: COSV58891064; COSMIC: COSV58891064;