rs1131118

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002117.6(HLA-C):c.361A>T(p.Arg121Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.047 ( 382 hom., cov: 5)

Exomes 𝑓: 0.17 ( 43773 hom. )

Consequence

HLA-C
NM_002117.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -10.4

Publications

28 publications found

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:

ENSG00000298396 (HGNC:):

ENSG00000298396 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005865842).

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-C	NM_002117.6 link	c.361A>T	p.Arg121Trp	missense_variant	Exon 3 of 8	ENST00000376228.10	NP_002108.4	P10321-1Q6R739Q95HC2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-C	ENST00000376228.10 link	c.361A>T	p.Arg121Trp	missense_variant	Exon 3 of 8	6	NM_002117.6	ENSP00000365402.5		P10321-1

Frequencies

GnomAD3 genomes

AF:

0.0470

AC:

2593

AN:

55198

Hom.:

377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0381

Gnomad AMR

AF:

0.0400

Gnomad ASJ

AF:

0.0800

Gnomad EAS

AF:

0.0327

Gnomad SAS

AF:

0.0327

Gnomad FIN

AF:

0.0203

Gnomad MID

AF:

0.0714

Gnomad NFE

AF:

0.0306

Gnomad OTH

AF:

0.0550

GnomAD2 exomes

AF:

0.249

AC:

58162

AN:

233900

AF XY:

0.252

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.228

Gnomad ASJ exome

AF:

0.403

Gnomad EAS exome

AF:

0.288

Gnomad FIN exome

AF:

0.186

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.273

GnomAD4 exome

AF:

0.173

AC:

138543

AN:

801260

Hom.:

43773

Cov.:

AF XY:

0.183

AC XY:

73945

AN XY:

404564

show subpopulations

African (AFR)

AF:

0.274

AC:

4514

AN:

16452

American (AMR)

AF:

0.277

AC:

7209

AN:

25988

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

5123

AN:

11740

East Asian (EAS)

AF:

0.374

AC:

6968

AN:

18624

South Asian (SAS)

AF:

0.292

AC:

16182

AN:

55486

European-Finnish (FIN)

AF:

0.129

AC:

3409

AN:

26528

Middle Eastern (MID)

AF:

0.319

AC:

712

AN:

2234

European-Non Finnish (NFE)

AF:

0.144

AC:

88267

AN:

611698

Other (OTH)

AF:

0.189

AC:

6159

AN:

32510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

2475

4951

7426

9902

12377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2148

4296

6444

8592

10740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0472

AC:

2609

AN:

55244

Hom.:

382

Cov.:

AF XY:

0.0464

AC XY:

1226

AN XY:

26416

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.104

AC:

1207

AN:

11572

American (AMR)

AF:

0.0400

AC:

202

AN:

5050

Ashkenazi Jewish (ASJ)

AF:

0.0800

AC:

AN:

650

East Asian (EAS)

AF:

0.0329

AC:

AN:

1398

South Asian (SAS)

AF:

0.0325

AC:

AN:

1506

European-Finnish (FIN)

AF:

0.0203

AC:

AN:

4182

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0306

AC:

912

AN:

29788

Other (OTH)

AF:

0.0565

AC:

AN:

620

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.317

Heterozygous variant carriers

151

302

452

603

754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.178

Hom.:

460

ESP6500AA

AF:

0.224

AC:

967

ESP6500EA

AF:

0.229

AC:

1933

ExAC

AF:

0.245

AC:

29468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.33

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.017

T;T

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-1.0

PhyloP100

-10

PrimateAI

Benign

0.22

PROVEAN

Benign

0.94

N;N

REVEL

Benign

0.22

Sift

Benign

0.28

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.030

B;B

Vest4

0.067

MPC

0.53

ClinPred

0.015

GERP RS

-5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

gMVP

0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over