rs3827077

chr20-3740809-C-T

Variant summary

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

The NM_052970.5(HSPA12B):c.44-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,611,748 control chromosomes in the GnomAD database, including 34,307 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4653 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29654 hom.)
• Consequence: HSPA12B NM_052970.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001956
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA12B	NM_052970.5	c.44-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000254963.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA12B	ENST00000254963.7	c.44-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_052970.5	P1
HSPA12B	ENST00000399701.1	c.-117-1475C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35293 AN: 152014 Hom.: 4642 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0913

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.247

GnomAD3 exomes AF: 0.192 AC: 47342 AN: 246560 Hom.: 4889 AF XY: 0.190 AC XY: 25414 AN XY: 133690

Gnomad AFR exome AF: 0.350

Gnomad AMR exome AF: 0.201

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.134

Gnomad SAS exome AF: 0.212

Gnomad FIN exome AF: 0.0925

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.197 AC: 287752 AN: 1459614 Hom.: 29654 Cov.: 32 AF XY: 0.197 AC XY: 142789 AN XY: 726006

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.0981

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.232 AC: 35330 AN: 152134 Hom.: 4653 Cov.: 32 AF XY: 0.226 AC XY: 16791 AN XY: 74380

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.0913

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.251

Alfa AF: 0.214 Hom.: 2652

Bravo AF: 0.249

Asia WGS AF: 0.219 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	11
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00020
dbscSNV1_RF	Benign	0.016
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: rs3827077; hg19: chr20-3721456; COSMIC: COSV54767159;