Variant rs1050414 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002117.6(HLA-C):c.213G>C(p.Pro71=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,460,664 control chromosomes in the GnomAD database, including 30,929 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 0.17 ( 3367 hom., cov: 15)

Exomes 𝑓: 0.12 ( 27562 hom. )

Consequence

HLA-C
NM_002117.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.822

Variant links:

Genes affected

HLA-C (HGNC:4933): (major histocompatibility complex, class I, C) HLA-C belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. About 6000 HLA-C alleles have been described. The HLA system plays an important role in the occurrence and outcome of infectious diseases, including those caused by the malaria parasite, the human immunodeficiency virus (HIV), and the severe acute respiratory syndrome coronavirus (SARS-CoV). The structural spike and the nucleocapsid proteins of the novel coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), are reported to contain multiple Class I epitopes with predicted HLA restrictions. Individual HLA genetic variation may help explain different immune responses to a virus across a population.[provided by RefSeq, Aug 2020]

HLA-C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP7

Synonymous conserved (PhyloP=-0.822 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-C	NM_002117.6 linkuse as main transcript	c.213G>C	p.Pro71=	synonymous_variant	2/8	ENST00000376228.10	NP_002108.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-C	ENST00000376228.10 linkuse as main transcript	c.213G>C	p.Pro71=	synonymous_variant	2/8		NM_002117.6	ENSP00000365402	P4	P10321-1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

16494

AN:

98442

Hom.:

3363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.0747

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.245

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.163

GnomAD3 exomes

AF:

0.0978

AC:

24453

AN:

250010

Hom.:

1373

AF XY:

0.101

AC XY:

13716

AN XY:

135470

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.0556

Gnomad ASJ exome

AF:

0.119

Gnomad EAS exome

AF:

0.0413

Gnomad SAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.0784

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.123

AC:

167836

AN:

1362158

Hom.:

27562

Cov.:

AF XY:

0.124

AC XY:

84417

AN XY:

679452

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.0650

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.0351

Gnomad4 SAS exome

AF:

0.151

Gnomad4 FIN exome

AF:

0.0960

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.130

GnomAD4 genome

AF:

0.168

AC:

16501

AN:

98506

Hom.:

3367

Cov.:

AF XY:

0.170

AC XY:

8076

AN XY:

47472

show subpopulations

Gnomad4 AFR

AF:

0.225

Gnomad4 AMR

AF:

0.135

Gnomad4 ASJ

AF:

0.161

Gnomad4 EAS

AF:

0.0750

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.134

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.114

Hom.:

457

Asia WGS

AF:

0.110

AC:

383

AN:

3478

EpiCase

AF:

0.115

EpiControl

AF:

0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.75

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

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