6-29942488-G-T

Variant names:

• chr6-29942488-G-T
• rs41545520
• ENST00000706894.1:c.-66G>T

Variant summary

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

The ENST00000706894.1(HLA-A):​c.-66G>T variant causes a 5 prime UTR 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 0.065 (848 hom., cov: 18)
  • Exomes 𝑓: 0.092 (10429 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-A ENST00000706894.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.96
• 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]

ENSG00000227766 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000706894.1. 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
	HLA-A	NM_002116.8	MANE Select	c.-66G>T		upstream_gene	N/A	NP_002107.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-A	ENST00000706894.1		c.-66G>T		5_prime_UTR	Exon 2 of 8	ENSP00000516610.1	A0A9L9PYF9
	HLA-A	ENST00000376806.9	TSL:6	c.-66G>T		5_prime_UTR	Exon 1 of 8	ENSP00000366002.5	Q5SRN5
	HLA-A	ENST00000706898.1		c.-66G>T		5_prime_UTR	Exon 2 of 9	ENSP00000516611.1	Q5SRN5

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 7782 AN: 120270 Hom.: 848 Cov.: 18

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.0558

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0452

Gnomad MID AF: 0.0634

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.0620

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0918 AC: 67988 AN: 740662 Hom.: 10429 Cov.: 10 AF XY: 0.0965 AC XY: 36537 AN XY: 378478

African (AFR) AF: 0.0135 AC: 238 AN: 17574

American (AMR) AF: 0.0618 AC: 1177 AN: 19054

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 1077 AN: 13202

East Asian (EAS) AF: 0.256 AC: 6087 AN: 23750

South Asian (SAS) AF: 0.192 AC: 10266 AN: 53458

European-Finnish (FIN) AF: 0.0566 AC: 1866 AN: 32992

Middle Eastern (MID) AF: 0.0912 AC: 293 AN: 3212

European-Non Finnish (NFE) AF: 0.0806 AC: 43848 AN: 544178

Other (OTH) AF: 0.0943 AC: 3136 AN: 33242

GnomAD4 genome AF: 0.0646 AC: 7778 AN: 120354 Hom.: 848 Cov.: 18 AF XY: 0.0682 AC XY: 3945 AN XY: 57838

African (AFR) AF: 0.0150 AC: 497 AN: 33160

American (AMR) AF: 0.0557 AC: 603 AN: 10834

Ashkenazi Jewish (ASJ) AF: 0.0666 AC: 192 AN: 2882

East Asian (EAS) AF: 0.330 AC: 1290 AN: 3906

South Asian (SAS) AF: 0.197 AC: 750 AN: 3812

European-Finnish (FIN) AF: 0.0452 AC: 347 AN: 7680

Middle Eastern (MID) AF: 0.0645 AC: 16 AN: 248

European-Non Finnish (NFE) AF: 0.0702 AC: 3893 AN: 55486

Other (OTH) AF: 0.0628 AC: 100 AN: 1592

Alfa AF: 0.0361 Hom.: 46

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.8
DANN	Benign	0.62
PhyloP100		-5.0
PromoterAI		-0.32	Neutral
Mutation Taster		=294/6	polymorphism (auto)

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: rs41545520; hg19: chr6-29910265;