rs1655900

Variant names:

• chr6-29948841-G-A
• rs1655900
• ENST00000706902.1:n.*1066G>A

Variant summary

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

The ENST00000706902.1(HLA-A):​n.*1066G>A 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 0.14 in 124,672 control chromosomes in the GnomAD database, including 1,231 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 0.14 (1231 hom., cov: 30)
• Consequence: HLA-A ENST00000706902.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.97
• Publications: 27 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 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.*1066G>A		non_coding_transcript_exon_variant	Exon 10 of 10			ENSP00000516613.1
HLA-A	ENST00000706903.1	n.*338G>A		non_coding_transcript_exon_variant	Exon 11 of 11			ENSP00000516614.1
HLA-A	ENST00000706904.1	c.*1152G>A		3_prime_UTR_variant	Exon 9 of 9			ENSP00000516615.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 17505 AN: 124618 Hom.: 1230 Cov.: 30

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0949

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.140 AC: 17502 AN: 124672 Hom.: 1231 Cov.: 30 AF XY: 0.134 AC XY: 8171 AN XY: 61176

African (AFR) AF: 0.109 AC: 2997 AN: 27600

American (AMR) AF: 0.0947 AC: 1113 AN: 11754

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 420 AN: 2784

East Asian (EAS) AF: 0.0246 AC: 95 AN: 3864

South Asian (SAS) AF: 0.166 AC: 622 AN: 3738

European-Finnish (FIN) AF: 0.0811 AC: 826 AN: 10180

Middle Eastern (MID) AF: 0.173 AC: 38 AN: 220

European-Non Finnish (NFE) AF: 0.178 AC: 11014 AN: 61960

Other (OTH) AF: 0.132 AC: 222 AN: 1678

Alfa AF: 0.149 Hom.: 2344

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.041
DANN	Benign	0.70
PhyloP100		-3.0

Splicing

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

Other links and lift over

dbSNP: rs1655900; hg19: chr6-29916618;