rs1131151

Variant names:

• chr6-31271853-C-A
• rs1131151
• NM_002117.6:c.89G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31271853-C-A
• chr6-31271853-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002117.6(HLA-C):​c.89G>T​(p.Arg30Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. 13/20 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 0.0 (0 hom., cov: 12)
  • Exomes 𝑓: 0.0000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-C NM_002117.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.481
• Publications: 13 publications found

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]

ENSG00000288813 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-C	NM_002117.6	c.89G>T	p.Arg30Met	missense_variant	Exon 2 of 8	ENST00000376228.10	NP_002108.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-C	ENST00000376228.10	c.89G>T	p.Arg30Met	missense_variant	Exon 2 of 8	6	NM_002117.6	ENSP00000365402.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 86092 Hom.: 0 Cov.: 12

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000843 AC: 2 AN: 237132 AF XY: 0.0000154

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000168 AC: 2 AN: 1190084 Hom.: 0 Cov.: 36 AF XY: 0.00000168 AC XY: 1 AN XY: 594534

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

African (AFR) AF: 0.00 AC: 0 AN: 24582

American (AMR) AF: 0.00 AC: 0 AN: 36034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20748

East Asian (EAS) AF: 0.0000366 AC: 1 AN: 27294

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3774

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 914568

Other (OTH) AF: 0.00 AC: 0 AN: 48234

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 86092 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 41232

African (AFR) AF: 0.00 AC: 0 AN: 20688

American (AMR) AF: 0.00 AC: 0 AN: 7516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1648

East Asian (EAS) AF: 0.00 AC: 0 AN: 2018

South Asian (SAS) AF: 0.00 AC: 0 AN: 2500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 188

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 44196

Other (OTH) AF: 0.00 AC: 0 AN: 1058

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.82
DEOGEN2	Benign	0.071	T;.
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.27	T;T
M_CAP	Benign	0.0035	T
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-1.0	T
PhyloP100		0.48
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.83	P;P
Vest4		0.55
MutPred		0.72		Loss of methylation at R30 (P = 0.0343);Loss of methylation at R30 (P = 0.0343);
MVP		0.28
MPC		0.96
ClinPred		0.64	D
GERP RS		1.4
PromoterAI		0.056	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.47
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1131151; hg19: chr6-31239630;