6-29948728-C-T

Variant names:

• chr6-29948728-C-T
• rs417162
• ENST00000706902.1:n.*953C>T

Variant summary

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

The ENST00000706902.1(HLA-A):​n.*953C>T 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 0.659 in 151,216 control chromosomes in the GnomAD database, including 32,455 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 0.66 (32455 hom., cov: 33)
• Consequence: HLA-A ENST00000706902.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 23 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 (AMR) allele frequency at 95% confidence interval = 0.744 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.*953C>T		non_coding_transcript_exon_variant	Exon 10 of 10			ENSP00000516613.1
HLA-A	ENST00000706904.1	c.*1039C>T		3_prime_UTR_variant	Exon 9 of 9			ENSP00000516615.1
HLA-A	ENST00000706902.1	n.*953C>T		3_prime_UTR_variant	Exon 10 of 10			ENSP00000516613.1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 99601 AN: 151094 Hom.: 32396 Cov.: 33

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.659 AC: 99713 AN: 151216 Hom.: 32455 Cov.: 33 AF XY: 0.659 AC XY: 48721 AN XY: 73916

African (AFR) AF: 0.714 AC: 29230 AN: 40918

American (AMR) AF: 0.755 AC: 11495 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2414 AN: 3446

East Asian (EAS) AF: 0.689 AC: 3553 AN: 5160

South Asian (SAS) AF: 0.629 AC: 3030 AN: 4816

European-Finnish (FIN) AF: 0.605 AC: 6385 AN: 10546

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41456 AN: 67808

Other (OTH) AF: 0.678 AC: 1423 AN: 2100

Alfa AF: 0.655 Hom.: 24925

Asia WGS AF: 0.715 AC: 2485 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	4.9
DANN	Benign	0.59
PhyloP100		-0.53

Splicing

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

Other links and lift over

dbSNP: rs417162; hg19: chr6-29916505;