NM_002117.6:c.620-56C>G

Variant names:

• chr6-31270541-G-C
• rs9264638
• NM_002117.6:c.620-56C>G

Variant summary

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

The NM_002117.6(HLA-C):​c.620-56C>G variant causes a intron 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: 2)
  • Exomes 𝑓: 0.0000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-C NM_002117.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 27 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002117.6. 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.620-56C>G		intron	N/A	NP_002108.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-C	ENST00000376228.10	TSL:6 MANE Select	c.620-56C>G		intron	N/A	ENSP00000365402.5
	HLA-C	ENST00000383329.7	TSL:6	c.620-56C>G		intron	N/A	ENSP00000372819.3
	HLA-C	ENST00000415537.1	TSL:6	c.617-56C>G		intron	N/A	ENSP00000400410.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 56076 Hom.: 0 Cov.: 2

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 AF: 0.00000428 AC: 3 AN: 700142 Hom.: 0 Cov.: 10 AF XY: 0.00000578 AC XY: 2 AN XY: 345760

African (AFR) AF: 0.00 AC: 0 AN: 11546

American (AMR) AF: 0.00 AC: 0 AN: 17288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6020

East Asian (EAS) AF: 0.0000906 AC: 1 AN: 11040

South Asian (SAS) AF: 0.00 AC: 0 AN: 33294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1870

European-Non Finnish (NFE) AF: 0.00000177 AC: 1 AN: 565896

Other (OTH) AF: 0.0000360 AC: 1 AN: 27756

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 56076 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 26620

African (AFR) AF: 0.00 AC: 0 AN: 10906

American (AMR) AF: 0.00 AC: 0 AN: 4944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 750

East Asian (EAS) AF: 0.00 AC: 0 AN: 1412

South Asian (SAS) AF: 0.00 AC: 0 AN: 1516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 98

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 31314

Other (OTH) AF: 0.00 AC: 0 AN: 658

Alfa AF: 0.00 Hom.: 1224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.9
DANN	Benign	0.51
PhyloP100		-1.3

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: rs9264638; hg19: chr6-31238318;