rs910652

Variant names:

• chr20-3747323-T-C
• rs910652
• NM_052970.5:c.676-894T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HSPA12B	NM_052970.5	c.676-894T>C		intron_variant	Intron 7 of 12	ENST00000254963.7	NP_443202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA12B	ENST00000254963.7	c.676-894T>C		intron_variant	Intron 7 of 12	1	NM_052970.5	ENSP00000254963.2
HSPA12B	ENST00000399701.1	c.418-894T>C		intron_variant	Intron 6 of 11	1		ENSP00000382608.1

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

African (AFR) AF: 0.269 AC: 11160 AN: 41472

American (AMR) AF: 0.286 AC: 4371 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1138 AN: 3472

East Asian (EAS) AF: 0.146 AC: 755 AN: 5162

South Asian (SAS) AF: 0.298 AC: 1435 AN: 4816

European-Finnish (FIN) AF: 0.237 AC: 2509 AN: 10588

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.329 AC: 22389 AN: 67954

Other (OTH) AF: 0.311 AC: 654 AN: 2106

Alfa AF: 0.319 Hom.: 13052

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
PhyloP100		-0.048
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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