rs9260100

Positions:

• chr6-29941765-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The XR_007059541.1(LOC124901298):​n.813+3016T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 151,258 control chromosomes in the GnomAD database, including 496 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 (496 hom., cov: 34)
• Consequence: LOC124901298 XR_007059541.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500

Genes affected

LOC124901298 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124901298	XR_007059541.1	n.813+3016T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-A	ENST00000396634.5	c.-281-201A>G		intron_variant				ENSP00000379873	P3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19565 AN: 151138 Hom.: 492 Cov.: 34

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0890

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.130 AC: 19613 AN: 151258 Hom.: 496 Cov.: 34 AF XY: 0.129 AC XY: 9575 AN XY: 73970

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.0890

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.143

Alfa AF: 0.115 Hom.: 48

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.36		Position offset: -1

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

Publications

LitVar

Other links and lift over

dbSNP: rs9260100; hg19: chr6-29909542; COSMIC: COSV65139499; COSMIC: COSV65139499;