Variant chr6-29945290-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002116.8(HLA-A):c.1093+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.37 ( 5969 hom., cov: 11)

Exomes 𝑓: 0.30 ( 53213 hom. )

Failed GnomAD Quality Control

Consequence

HLA-A
NM_002116.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.392

Variant links:

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]

HLA-A links:

HLA-A (HGNC:):

HLA-A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 6-29945290-T-C is Benign according to our data. Variant chr6-29945290-T-C is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-A	NM_002116.8 linkuse as main transcript	c.1093+9T>C		intron_variant		ENST00000376809.10	NP_002107.3	P04439-1B1PKY1B2R7U3
LOC124901298	XR_007059541.1 linkuse as main transcript	n.304A>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-A	ENST00000376809.10 linkuse as main transcript	c.1093+9T>C		intron_variant		6	NM_002116.8	ENSP00000366005.5		P04439-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

25736

AN:

70498

Hom.:

5940

Cov.:

FAILED QC

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.438

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.388

GnomAD3 exomes

AF:

0.531

AC:

128321

AN:

241530

Hom.:

34744

AF XY:

0.524

AC XY:

68223

AN XY:

130238

show subpopulations

Gnomad AFR exome

AF:

0.585

Gnomad AMR exome

AF:

0.635

Gnomad ASJ exome

AF:

0.559

Gnomad EAS exome

AF:

0.508

Gnomad SAS exome

AF:

0.468

Gnomad FIN exome

AF:

0.518

Gnomad NFE exome

AF:

0.514

Gnomad OTH exome

AF:

0.506

GnomAD4 exome

AF:

0.299

AC:

195621

AN:

653572

Hom.:

53213

Cov.:

AF XY:

0.306

AC XY:

103262

AN XY:

337954

show subpopulations

Gnomad4 AFR exome

AF:

0.427

Gnomad4 AMR exome

AF:

0.563

Gnomad4 ASJ exome

AF:

0.417

Gnomad4 EAS exome

AF:

0.519

Gnomad4 SAS exome

AF:

0.380

Gnomad4 FIN exome

AF:

0.286

Gnomad4 NFE exome

AF:

0.246

Gnomad4 OTH exome

AF:

0.352

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.365

AC:

25789

AN:

70564

Hom.:

5969

Cov.:

AF XY:

0.355

AC XY:

11965

AN XY:

33696

show subpopulations

Gnomad4 AFR

AF:

0.478

Gnomad4 AMR

AF:

0.466

Gnomad4 ASJ

AF:

0.422

Gnomad4 EAS

AF:

0.415

Gnomad4 SAS

AF:

0.370

Gnomad4 FIN

AF:

0.187

Gnomad4 NFE

AF:

0.287

Gnomad4 OTH

AF:

0.388

Alfa

AF:

0.495

Hom.:

13668

Asia WGS

AF:

0.464

AC:

1612

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.7

DANN

Benign

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over