rs910652

Positions:

• chr20-3747323-T-C

Variant summary

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

The NM_052970.5(HSPA12B):​c.676-894T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,066 control chromosomes in the GnomAD database, including 6,893 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 0.30 (6893 hom., cov: 32)
• Consequence: HSPA12B NM_052970.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA12B	NM_052970.5	c.676-894T>C		intron_variant		ENST00000254963.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA12B	ENST00000254963.7	c.676-894T>C		intron_variant		1	NM_052970.5	P1
HSPA12B	ENST00000399701.1	c.418-894T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45024 AN: 151948 Hom.: 6890 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.307

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.296 AC: 45055 AN: 152066 Hom.: 6893 Cov.: 32 AF XY: 0.290 AC XY: 21527 AN XY: 74320

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.311

Alfa AF: 0.321 Hom.: 10480

Bravo AF: 0.299

Asia WGS AF: 0.255 AC: 885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.65

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: rs910652; hg19: chr20-3727970; COSMIC: COSV54769388;