rs67384697

Variant names:

• chr6-31268905-AC-A
• rs67384697
• NM_002117.6:c.*263delG

Your query was ambiguous. Multiple possible variants found:

• chr6-31268905-AC-A
• chr6-31268905-AC-ACC

Variant summary

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

The NM_002117.6(HLA-C):​c.*263delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 18)
  • Exomes 𝑓: 0.00037 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-C NM_002117.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 26 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]

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.*263delG		3_prime_UTR_variant	Exon 8 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.*263delG		3_prime_UTR_variant	Exon 8 of 8	6	NM_002117.6	ENSP00000365402.5

Frequencies

GnomAD3 genomes AF: 0.000636 AC: 40 AN: 62914 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.000251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000482

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: 0.00112

Gnomad OTH AF: 0.00131

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000371 AC: 60 AN: 161788 Hom.: 0 Cov.: 0 AF XY: 0.000375 AC XY: 31 AN XY: 82566

⚠️ 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: 5110

American (AMR) AF: 0.000859 AC: 5 AN: 5818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3950

East Asian (EAS) AF: 0.00 AC: 0 AN: 11816

South Asian (SAS) AF: 0.00 AC: 0 AN: 8276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 772

European-Non Finnish (NFE) AF: 0.000519 AC: 53 AN: 102130

Other (OTH) AF: 0.000198 AC: 2 AN: 10120

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000635 AC: 40 AN: 63004 Hom.: 0 Cov.: 18 AF XY: 0.000451 AC XY: 14 AN XY: 31014

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

African (AFR) AF: 0.000250 AC: 4 AN: 16020

American (AMR) AF: 0.000480 AC: 3 AN: 6244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 712

East Asian (EAS) AF: 0.00 AC: 0 AN: 2736

South Asian (SAS) AF: 0.00 AC: 0 AN: 1438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 80

European-Non Finnish (NFE) AF: 0.00111 AC: 32 AN: 28700

Other (OTH) AF: 0.00127 AC: 1 AN: 786

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.296 Hom.: 710

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs67384697; hg19: chr6-31236682; COSMIC: COSV66111667; COSMIC: COSV66111667;