Variant rs6076550 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.00

Variant links:

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]

HSPA12B links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
HSPA12B	NM_052970.5 linkuse as main transcript	c.562C>T	p.Leu188Leu	synonymous_variant	7/13	ENST00000254963.7	NP_443202.3	Q96MM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA12B	ENST00000254963.7 linkuse as main transcript	c.562C>T	p.Leu188Leu	synonymous_variant	7/13	1	NM_052970.5	ENSP00000254963.2		Q96MM6
HSPA12B	ENST00000399701.1 linkuse as main transcript	c.304C>T	p.Leu102Leu	synonymous_variant	6/12	1		ENSP00000382608.1		Q5JX83

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2740

AN:

152238

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0188

AC XY:

2557

AN XY:

135864

show subpopulations

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.:

AF XY:

0.0184

AC XY:

13399

AN XY:

727054

show subpopulations

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.:

Cov.:

AF XY:

0.0175

AC XY:

1305

AN XY:

74504

show subpopulations

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.:

Bravo

AF:

0.0175

Asia WGS

AF:

0.0260

AC:

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over