chr6-29944050-G-A

Position:

• chr6-29944050-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002116.8(HLA-A):​c.620-72G>A variant causes a intron 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 0.0025 (1 hom., cov: 14)
  • Exomes 𝑓: 0.0061 (9 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-A NM_002116.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS2: High AC in GnomAd4 at 196 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-A	NM_002116.8	c.620-72G>A		intron_variant		ENST00000376809.10	NP_002107.3
LOC124901298	XR_007059541.1	n.813+731C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-A	ENST00000376809.10	c.620-72G>A		intron_variant			NM_002116.8	ENSP00000366005	P3

Frequencies

GnomAD3 genomes AF: 0.00238 AC: 187 AN: 78588 Hom.: 1 Cov.: 14

Gnomad AFR AF: 0.00221

Gnomad AMI AF: 0.00169

Gnomad AMR AF: 0.00394

Gnomad ASJ AF: 0.00420

Gnomad EAS AF: 0.00753

Gnomad SAS AF: 0.00280

Gnomad FIN AF: 0.000992

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00201

Gnomad OTH AF: 0.00199

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00611 AC: 6532 AN: 1069584 Hom.: 9 AF XY: 0.00697 AC XY: 3704 AN XY: 531488

Gnomad4 AFR exome AF: 0.0130

Gnomad4 AMR exome AF: 0.0271

Gnomad4 ASJ exome AF: 0.0175

Gnomad4 EAS exome AF: 0.0113

Gnomad4 SAS exome AF: 0.0237

Gnomad4 FIN exome AF: 0.00398

Gnomad4 NFE exome AF: 0.00361

Gnomad4 OTH exome AF: 0.00946

GnomAD4 genome AF: 0.00249 AC: 196 AN: 78612 Hom.: 1 Cov.: 14 AF XY: 0.00251 AC XY: 96 AN XY: 38270

Gnomad4 AFR AF: 0.00231

Gnomad4 AMR AF: 0.00411

Gnomad4 ASJ AF: 0.00420

Gnomad4 EAS AF: 0.00756

Gnomad4 SAS AF: 0.00322

Gnomad4 FIN AF: 0.000992

Gnomad4 NFE AF: 0.00201

Gnomad4 OTH AF: 0.00684

Alfa AF: 0.310 Hom.: 1626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.8
DANN	Benign	0.80

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: rs9260168; hg19: chr6-29911827; COSMIC: COSV65143335; COSMIC: COSV65143335;