Variant 6-31271305-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_002117.6(HLA-C):c.387C>G(p.Pro129Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.0019 ( 1 hom., cov: 6)

Exomes 𝑓: 0.0073 ( 287 hom. )

Failed GnomAD Quality Control

Consequence

HLA-C
NM_002117.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.48

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:

HLA-C (HGNC:):

HLA-C links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP7

Synonymous conserved (PhyloP=-6.48 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-C	NM_002117.6 linkuse as main transcript	c.387C>G	p.Pro129Pro	synonymous_variant	3/8	ENST00000376228.10	NP_002108.4	P10321-1Q6R739Q95HC2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-C	ENST00000376228.10 linkuse as main transcript	c.387C>G	p.Pro129Pro	synonymous_variant	3/8	6	NM_002117.6	ENSP00000365402.5		P10321-1

Frequencies

GnomAD3 genomes

AF:

0.00194

AC:

121

AN:

62276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00415

Gnomad AMI

AF:

0.00655

Gnomad AMR

AF:

0.00213

Gnomad ASJ

AF:

0.00227

Gnomad EAS

AF:

0.00665

Gnomad SAS

AF:

0.00238

Gnomad FIN

AF:

0.00163

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000734

Gnomad OTH

AF:

0.00535

GnomAD3 exomes

AF:

0.141

AC:

31387

AN:

222356

Hom.:

331

AF XY:

0.138

AC XY:

16781

AN XY:

121466

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.201

Gnomad ASJ exome

AF:

0.231

Gnomad EAS exome

AF:

0.0743

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00729

AC:

7209

AN:

988374

Hom.:

287

Cov.:

AF XY:

0.00795

AC XY:

3941

AN XY:

495880

show subpopulations

Gnomad4 AFR exome

AF:

0.0250

Gnomad4 AMR exome

AF:

0.0193

Gnomad4 ASJ exome

AF:

0.0276

Gnomad4 EAS exome

AF:

0.0254

Gnomad4 SAS exome

AF:

0.0285

Gnomad4 FIN exome

AF:

0.00371

Gnomad4 NFE exome

AF:

0.00360

Gnomad4 OTH exome

AF:

0.0124

GnomAD4 genome

AF:

0.00193

AC:

120

AN:

62308

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

AN XY:

29720

show subpopulations

Gnomad4 AFR

AF:

0.00406

Gnomad4 AMR

AF:

0.00213

Gnomad4 ASJ

AF:

0.00227

Gnomad4 EAS

AF:

0.00670

Gnomad4 SAS

AF:

0.00238

Gnomad4 FIN

AF:

0.00163

Gnomad4 NFE

AF:

0.000734

Gnomad4 OTH

AF:

0.00529

Alfa

AF:

0.130

Hom.:

Asia WGS

AF:

0.186

AC:

648

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

9.8

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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