chr6-29941649-T-C

Variant names:

• chr6-29941649-T-C
• rs9260090

Variant summary

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

The variant allele was found at a frequency of 0.132 in 151,432 control chromosomes in the GnomAD database, including 548 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 0.13 (548 hom., cov: 35)
• Consequence: HCG4P5 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 2 publications found

Genes affected

HCG4P5 (HGNC:22925): (HLA complex group 4 pseudogene 5)

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000396634.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-A	ENST00000396634.5	TSL:6	c.-281-317T>C		intron	N/A	ENSP00000379873.1
	POLR1HASP	ENST00000849679.1		n.66-13103A>G		intron	N/A
	POLR1HASP	ENST00000849682.1		n.751-13103A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20000 AN: 151318 Hom.: 543 Cov.: 35

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.132 AC: 20047 AN: 151432 Hom.: 548 Cov.: 35 AF XY: 0.132 AC XY: 9785 AN XY: 74030

African (AFR) AF: 0.179 AC: 7332 AN: 41070

American (AMR) AF: 0.147 AC: 2237 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3454

East Asian (EAS) AF: 0.124 AC: 635 AN: 5140

South Asian (SAS) AF: 0.165 AC: 792 AN: 4786

European-Finnish (FIN) AF: 0.0891 AC: 943 AN: 10588

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.106 AC: 7224 AN: 67862

Other (OTH) AF: 0.144 AC: 303 AN: 2100

Alfa AF: 0.116 Hom.: 50

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.46
PhyloP100		0.068
PromoterAI		0.027	Neutral
Mutation Taster		=100/0	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: rs9260090; hg19: chr6-29909426;