rs2074491

Variant names:

• chr6-31272119-T-A
• rs2074491
• ENST00000495835.1:n.12A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31272119-T-A
• chr6-31272119-T-C
• chr6-31272119-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000495835.1(HLA-C):​n.12A>T variant causes a non coding transcript exon 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: not found (cov: 15)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HLA-C ENST00000495835.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-C	NM_002117.6	c.-48A>T		upstream_gene_variant		ENST00000376228.10	NP_002108.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-C	ENST00000376228.10	c.-48A>T		upstream_gene_variant		6	NM_002117.6	ENSP00000365402.5

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD4 exome AF: 0.00000140 AC: 1 AN: 715056 Hom.: 0 Cov.: 10 AF XY: 0.00000277 AC XY: 1 AN XY: 360970

⚠️ 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: 14350

American (AMR) AF: 0.00 AC: 0 AN: 19358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11818

East Asian (EAS) AF: 0.00 AC: 0 AN: 18616

South Asian (SAS) AF: 0.00 AC: 0 AN: 51544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2514

European-Non Finnish (NFE) AF: 0.00000185 AC: 1 AN: 540228

Other (OTH) AF: 0.00 AC: 0 AN: 31460

⚠️ 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 Cov.: 15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.50
PhyloP100		-0.62
PromoterAI		0.065	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2074491; hg19: chr6-31239896;