6-29949108-T-C

Variant names:

• chr6-29949108-T-C
• rs9260313
• ENST00000706902.1:n.*1333T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000706902.1(HLA-A):​n.*1333T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 147,512 control chromosomes in the GnomAD database, including 14,229 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 0.42 (14229 hom., cov: 32)
• Consequence: HLA-A ENST00000706902.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510
• Publications: 15 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-A	ENST00000706902.1	n.*1333T>C		non_coding_transcript_exon_variant	Exon 10 of 10			ENSP00000516613.1
HLA-A	ENST00000706903.1	n.*605T>C		non_coding_transcript_exon_variant	Exon 11 of 11			ENSP00000516614.1
HLA-A	ENST00000706904.1	c.*1419T>C		3_prime_UTR_variant	Exon 9 of 9			ENSP00000516615.1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 62207 AN: 147388 Hom.: 14175 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.422 AC: 62322 AN: 147512 Hom.: 14229 Cov.: 32 AF XY: 0.422 AC XY: 30470 AN XY: 72168

African (AFR) AF: 0.592 AC: 23011 AN: 38854

American (AMR) AF: 0.525 AC: 7841 AN: 14938

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1802 AN: 3408

East Asian (EAS) AF: 0.403 AC: 2039 AN: 5060

South Asian (SAS) AF: 0.477 AC: 2268 AN: 4750

European-Finnish (FIN) AF: 0.262 AC: 2740 AN: 10462

Middle Eastern (MID) AF: 0.504 AC: 143 AN: 284

European-Non Finnish (NFE) AF: 0.319 AC: 21309 AN: 66798

Other (OTH) AF: 0.468 AC: 961 AN: 2052

Alfa AF: 0.376 Hom.: 1296

Asia WGS AF: 0.530 AC: 1840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.4
DANN	Benign	0.61
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs9260313; hg19: chr6-29916885;