rs6076550

Positions:

• chr20-3745918-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_052970.5(HSPA12B):​c.562C>T​(p.Leu188=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0181 in 1,613,808 control chromosomes in the GnomAD database, including 328 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 0.018 (22 hom., cov: 32)
  • Exomes 𝑓: 0.018 (306 hom.)
• Consequence: HSPA12B NM_052970.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00

Genes affected

HSPA12B (HGNC:16193): (heat shock protein family A (Hsp70) member 12B) The protein encoded by this gene contains an atypical heat shock protein 70 (Hsp70) ATPase domain and is therefore a distant member of the mammalian Hsp70 family. This gene may be involved in susceptibility to atherosclerosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.018 (2744/152356) while in subpopulation SAS AF= 0.0276 (133/4822). AF 95% confidence interval is 0.0238. There are 22 homozygotes in gnomad4. There are 1305 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA12B	NM_052970.5	c.562C>T	p.Leu188=	synonymous_variant	7/13	ENST00000254963.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA12B	ENST00000254963.7	c.562C>T	p.Leu188=	synonymous_variant	7/13	1	NM_052970.5	P1
HSPA12B	ENST00000399701.1	c.304C>T	p.Leu102=	synonymous_variant	6/12	1

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2740 AN: 152238 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.0188

Gnomad SAS AF: 0.0276

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0210

GnomAD3 exomes AF: 0.0182 AC: 4584 AN: 251336 Hom.: 57 AF XY: 0.0188 AC XY: 2557 AN XY: 135864

Gnomad AFR exome AF: 0.0160

Gnomad AMR exome AF: 0.0117

Gnomad ASJ exome AF: 0.0288

Gnomad EAS exome AF: 0.0213

Gnomad SAS exome AF: 0.0231

Gnomad FIN exome AF: 0.0108

Gnomad NFE exome AF: 0.0190

Gnomad OTH exome AF: 0.0223

GnomAD4 exome AF: 0.0181 AC: 26444 AN: 1461452 Hom.: 306 Cov.: 32 AF XY: 0.0184 AC XY: 13399 AN XY: 727054

Gnomad4 AFR exome AF: 0.0159

Gnomad4 AMR exome AF: 0.0125

Gnomad4 ASJ exome AF: 0.0279

Gnomad4 EAS exome AF: 0.0118

Gnomad4 SAS exome AF: 0.0239

Gnomad4 FIN exome AF: 0.0100

Gnomad4 NFE exome AF: 0.0181

Gnomad4 OTH exome AF: 0.0216

GnomAD4 genome AF: 0.0180 AC: 2744 AN: 152356 Hom.: 22 Cov.: 32 AF XY: 0.0175 AC XY: 1305 AN XY: 74504

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.0128

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.0185

Gnomad4 SAS AF: 0.0276

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0198 Hom.: 47

Bravo AF: 0.0175

Asia WGS AF: 0.0260 AC: 91 AN: 3478

EpiCase AF: 0.0215

EpiControl AF: 0.0210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6076550; hg19: chr20-3726565;