6-29949483-C-T

Variant names:

• chr6-29949483-C-T
• rs2517716
• ENST00000706904.1:c.*1794C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

POLR1HASP (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000706904.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-A	ENST00000706904.1		c.*1794C>T		3_prime_UTR	Exon 9 of 9	ENSP00000516615.1	A0A9L9PY26
	HLA-A	ENST00000706902.1		n.*1708C>T		non_coding_transcript_exon	Exon 10 of 10	ENSP00000516613.1	A0A9L9PY26
	HLA-A	ENST00000706903.1		n.*980C>T		non_coding_transcript_exon	Exon 11 of 11	ENSP00000516614.1	P04439-1

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

African (AFR) AF: 0.692 AC: 28503 AN: 41206

American (AMR) AF: 0.749 AC: 11423 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2404 AN: 3468

East Asian (EAS) AF: 0.683 AC: 3523 AN: 5160

South Asian (SAS) AF: 0.624 AC: 3001 AN: 4806

European-Finnish (FIN) AF: 0.604 AC: 6364 AN: 10530

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41233 AN: 67930

Other (OTH) AF: 0.663 AC: 1388 AN: 2094

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.3
DANN	Benign	0.67
PhyloP100		-0.31

Splicing

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

Other links and lift over

dbSNP: rs2517716; hg19: chr6-29917260;