rs2524094

Variant names:

• chr6-31272264-C-A
• rs2524094
• ENST00000692808.2:n.869C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31272264-C-A
• chr6-31272264-C-G
• chr6-31272264-C-T

Variant summary

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

The ENST00000692808.2(ENSG00000288813):​n.869C>A 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: 𝑓 0.0 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000288813 ENST00000692808.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219
• Publications: 28 publications found

Genes affected

ENSG00000288813 (HGNC:):

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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000692808.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-C	NM_002117.6	MANE Select	c.-193G>T		upstream_gene	N/A	NP_002108.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000288813	ENST00000692808.2		n.869C>A		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000298396	ENST00000755297.1		n.32+1158C>A		intron	N/A
	HLA-C	ENST00000376228.10	TSL:6 MANE Select	c.-193G>T		upstream_gene	N/A	ENSP00000365402.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 140552 Hom.: 0 Cov.: 20

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

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 284416 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 148794

African (AFR) AF: 0.00 AC: 0 AN: 8102

American (AMR) AF: 0.00 AC: 0 AN: 11638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8228

East Asian (EAS) AF: 0.00 AC: 0 AN: 15592

South Asian (SAS) AF: 0.00 AC: 0 AN: 35366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1214

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 173416

Other (OTH) AF: 0.00 AC: 0 AN: 16554

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 140552 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 67852

African (AFR) AF: 0.00 AC: 0 AN: 37010

American (AMR) AF: 0.00 AC: 0 AN: 13894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3350

East Asian (EAS) AF: 0.00 AC: 0 AN: 4616

South Asian (SAS) AF: 0.00 AC: 0 AN: 4336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65106

Other (OTH) AF: 0.00 AC: 0 AN: 1896

Alfa AF: 0.00 Hom.: 20638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		-0.22
PromoterAI		0.0024	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2524094; hg19: chr6-31240041;