20-3745918-C-T

Variant names:

• chr20-3745918-C-T
• rs6076550
• NM_052970.5:c.562C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001197327.2(HSPA12B):​c.559C>T​(p.Leu187Leu) variant causes a splice region, 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. 1/1 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 0.018 (22 hom., cov: 32)
  • Exomes 𝑓: 0.018 (306 hom.)
• Consequence: HSPA12B NM_001197327.2 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 7 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 -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001197327.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA12B	NM_052970.5	MANE Select	c.562C>T	p.Leu188Leu	synonymous	Exon 7 of 13	NP_443202.3
	HSPA12B	NM_001197327.2		c.559C>T	p.Leu187Leu	splice_region synonymous	Exon 7 of 13	NP_001184256.1	B7ZLP2
	HSPA12B	NM_001318322.2		c.304C>T	p.Leu102Leu	synonymous	Exon 6 of 12	NP_001305251.1	Q5JX83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA12B	ENST00000254963.7	TSL:1 MANE Select	c.562C>T	p.Leu188Leu	synonymous	Exon 7 of 13	ENSP00000254963.2	Q96MM6
	HSPA12B	ENST00000399701.1	TSL:1	c.304C>T	p.Leu102Leu	synonymous	Exon 6 of 12	ENSP00000382608.1	Q5JX83
	HSPA12B	ENST00000969453.1		c.584C>T	p.Ala195Val	missense	Exon 7 of 12	ENSP00000639512.1

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

GnomAD2 exomes AF: 0.0182 AC: 4584 AN: 251336 AF XY: 0.0188

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 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

African (AFR) AF: 0.0159 AC: 532 AN: 33470

American (AMR) AF: 0.0125 AC: 557 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 729 AN: 26132

East Asian (EAS) AF: 0.0118 AC: 469 AN: 39698

South Asian (SAS) AF: 0.0239 AC: 2060 AN: 86252

European-Finnish (FIN) AF: 0.0100 AC: 536 AN: 53348

Middle Eastern (MID) AF: 0.0322 AC: 186 AN: 5768

European-Non Finnish (NFE) AF: 0.0181 AC: 20070 AN: 1111680

Other (OTH) AF: 0.0216 AC: 1305 AN: 60382

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

African (AFR) AF: 0.0156 AC: 650 AN: 41584

American (AMR) AF: 0.0128 AC: 196 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3472

East Asian (EAS) AF: 0.0185 AC: 96 AN: 5192

South Asian (SAS) AF: 0.0276 AC: 133 AN: 4822

European-Finnish (FIN) AF: 0.0120 AC: 128 AN: 10624

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0205 AC: 1393 AN: 68040

Other (OTH) AF: 0.0208 AC: 44 AN: 2114

Alfa AF: 0.0192 Hom.: 84

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		4.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6076550; hg19: chr20-3726565;