6-29949483-C-T

Position:

• chr6-29949483-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000706904.1(HLA-A):​c.*1794C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 151,654 control chromosomes in the GnomAD database, including 32,398 homozygotes. 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 0.65 (32398 hom., cov: 31)
• Consequence: HLA-A ENST00000706904.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307

Genes affected

HLA-A (HGNC:4931): (major histocompatibility complex, class I, A) HLA-A 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 the endoplasmic reticulum lumen so that they can be recognized by cytotoxic T cells. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, 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. More than 6000 HLA-A 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.29949483C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-A	ENST00000706904.1	c.*1794C>T		3_prime_UTR_variant	9/9			ENSP00000516615.1
HLA-A	ENST00000706902.1	n.*1708C>T		non_coding_transcript_exon_variant	10/10			ENSP00000516613.1
HLA-A	ENST00000706903.1	n.*980C>T		non_coding_transcript_exon_variant	11/11			ENSP00000516614.1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98458 AN: 151538 Hom.: 32341 Cov.: 31

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.661

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.650 AC: 98566 AN: 151654 Hom.: 32398 Cov.: 31 AF XY: 0.650 AC XY: 48123 AN XY: 74054

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.663

Alfa AF: 0.548 Hom.: 2795

Bravo AF: 0.663

Asia WGS AF: 0.704 AC: 2427 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.3
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2517716; hg19: chr6-29917260;