rs1061235

chr6-29945521-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002116.8(HLA-A):c.*66A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.022 (3 hom., cov: 24)
  • Exomes 𝑓: 0.0054 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-A NM_002116.8 3_prime_UTR
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.347

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]

LOC124901298 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-A	NM_002116.8	c.*66A>T		3_prime_UTR_variant	8/8	ENST00000376809.10
LOC124901298	XR_007059541.1	n.73T>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-A	ENST00000376809.10	c.*66A>T		3_prime_UTR_variant	8/8		NM_002116.8	P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 3195 AN: 142960 Hom.: 3 Cov.: 24 FAILED QC

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.00444

Gnomad AMR AF: 0.0281

Gnomad ASJ AF: 0.0218

Gnomad EAS AF: 0.0415

Gnomad SAS AF: 0.0542

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.0428

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0242

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00536 AC: 4410 AN: 822874 Hom.: 4 Cov.: 12 AF XY: 0.00579 AC XY: 2478 AN XY: 428224

Gnomad4 AFR exome AF: 0.00870

Gnomad4 AMR exome AF: 0.00916

Gnomad4 ASJ exome AF: 0.00777

Gnomad4 EAS exome AF: 0.0272

Gnomad4 SAS exome AF: 0.0145

Gnomad4 FIN exome AF: 0.00631

Gnomad4 NFE exome AF: 0.00259

Gnomad4 OTH exome AF: 0.00579

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0224 AC: 3210 AN: 143072 Hom.: 3 Cov.: 24 AF XY: 0.0236 AC XY: 1639 AN XY: 69568

Gnomad4 AFR AF: 0.0285

Gnomad4 AMR AF: 0.0285

Gnomad4 ASJ AF: 0.0218

Gnomad4 EAS AF: 0.0414

Gnomad4 SAS AF: 0.0550

Gnomad4 FIN AF: 0.0261

Gnomad4 NFE AF: 0.0138

Gnomad4 OTH AF: 0.0239

Alfa AF: 0.0315 Hom.: 0

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Carbamazepine hypersensitivity Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.4
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1061235; hg19: chr6-29913298; COSMIC: COSV65139711; COSMIC: COSV65139711;