rs41545520

Variant names:

• chr6-29942488-G-A
• rs41545520
• ENST00000429656.1:n.580C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-29942488-G-A
• chr6-29942488-G-C
• chr6-29942488-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000429656.1(ENSG00000227766):​n.580C>T variant causes a non coding transcript exon 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 0.11 (9 hom., cov: 18)
  • Exomes 𝑓: 0.070 (497 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000227766 ENST00000429656.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.96
• Publications: 6 publications found

Genes affected

ENSG00000227766 (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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124901298	XR_007059541.1	n.813+2293C>T		intron_variant	Intron 1 of 2
HLA-A	NM_002116.8	c.-66G>A		upstream_gene_variant		ENST00000376809.10	NP_002107.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-A	ENST00000376809.10	c.-66G>A		upstream_gene_variant		6	NM_002116.8	ENSP00000366005.5

Frequencies

GnomAD3 genomes AF: 0.115 AC: 13395 AN: 116976 Hom.: 9 Cov.: 18

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0106

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.151

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.132

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0697 AC: 50473 AN: 724586 Hom.: 497 Cov.: 10 AF XY: 0.0711 AC XY: 26329 AN XY: 370134

African (AFR) AF: 0.201 AC: 3215 AN: 16020

American (AMR) AF: 0.202 AC: 3705 AN: 18358

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 1727 AN: 12852

East Asian (EAS) AF: 0.223 AC: 5215 AN: 23412

South Asian (SAS) AF: 0.131 AC: 6815 AN: 52026

European-Finnish (FIN) AF: 0.0330 AC: 1086 AN: 32866

Middle Eastern (MID) AF: 0.131 AC: 406 AN: 3092

European-Non Finnish (NFE) AF: 0.0474 AC: 25274 AN: 533494

Other (OTH) AF: 0.0933 AC: 3030 AN: 32466

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.115 AC: 13425 AN: 117062 Hom.: 9 Cov.: 18 AF XY: 0.115 AC XY: 6457 AN XY: 56282

African (AFR) AF: 0.211 AC: 6600 AN: 31332

American (AMR) AF: 0.160 AC: 1685 AN: 10528

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 352 AN: 2814

East Asian (EAS) AF: 0.159 AC: 611 AN: 3852

South Asian (SAS) AF: 0.143 AC: 532 AN: 3708

European-Finnish (FIN) AF: 0.0261 AC: 199 AN: 7636

Middle Eastern (MID) AF: 0.151 AC: 36 AN: 238

European-Non Finnish (NFE) AF: 0.0586 AC: 3204 AN: 54686

Other (OTH) AF: 0.131 AC: 198 AN: 1512

Alfa AF: 0.00359 Hom.: 46

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.5
DANN	Benign	0.84
PhyloP100		-5.0
PromoterAI		-0.30	Neutral
Mutation Taster		=294/6	polymorphism

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;