rs1071742

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002116.8(HLA-A):c.299T>A(p.Val100Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

Frequency

Genomes: 𝑓 0.20 ( 1011 hom., cov: 8)

Exomes 𝑓: 0.16 ( 21146 hom. )

Failed GnomAD Quality Control

Consequence

HLA-A
NM_002116.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.41

Publications

29 publications found

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:

ENSG00000227766 (HGNC:):

ENSG00000227766 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005369067).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002116.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-A	NM_002116.8	MANE Select	c.299T>A	p.Val100Glu	missense	Exon 2 of 8	NP_002107.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HLA-A	ENST00000376809.10	TSL:6 MANE Select	c.299T>A	p.Val100Glu	missense	Exon 2 of 8	ENSP00000366005.5	P04439-1
HLA-A	ENST00000952344.1		c.299T>A	p.Val100Glu	missense	Exon 2 of 8	ENSP00000622403.1
HLA-A	ENST00000706894.1		c.299T>A	p.Val100Glu	missense	Exon 3 of 8	ENSP00000516610.1	A0A9L9PYF9

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

12220

AN:

60812

Hom.:

1003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.0650

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.0448

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.235

GnomAD2 exomes

AF:

0.182

AC:

41399

AN:

227030

AF XY:

0.182

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.159

AC:

160527

AN:

1010210

Hom.:

21146

Cov.:

AF XY:

0.161

AC XY:

80828

AN XY:

502366

show subpopulations

African (AFR)

AF:

0.246

AC:

6111

AN:

24882

American (AMR)

AF:

0.261

AC:

7242

AN:

27766

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

3661

AN:

17684

East Asian (EAS)

AF:

0.254

AC:

5143

AN:

20268

South Asian (SAS)

AF:

0.202

AC:

13642

AN:

67472

European-Finnish (FIN)

AF:

0.0959

AC:

3377

AN:

35206

Middle Eastern (MID)

AF:

0.233

AC:

792

AN:

3400

European-Non Finnish (NFE)

AF:

0.147

AC:

113154

AN:

772326

Other (OTH)

AF:

0.180

AC:

7405

AN:

41206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

3307

6613

9920

13226

16533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4094

8188

12282

16376

20470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.201

AC:

12266

AN:

60878

Hom.:

1011

Cov.:

AF XY:

0.195

AC XY:

5787

AN XY:

29666

show subpopulations

African (AFR)

AF:

0.332

AC:

5722

AN:

17250

American (AMR)

AF:

0.279

AC:

1370

AN:

4906

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

296

AN:

1282

East Asian (EAS)

AF:

0.170

AC:

361

AN:

2128

South Asian (SAS)

AF:

0.202

AC:

399

AN:

1976

European-Finnish (FIN)

AF:

0.0448

AC:

214

AN:

4772

Middle Eastern (MID)

AF:

0.315

AC:

AN:

108

European-Non Finnish (NFE)

AF:

0.134

AC:

3654

AN:

27288

Other (OTH)

AF:

0.237

AC:

193

AN:

814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

305

611

916

1222

1527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.132

Hom.:

333

ExAC

AF:

0.173

AC:

21016

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.58

CADD

Benign

4.8

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.018

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0084

LIST_S2

Benign

0.027

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.92

PhyloP100

-4.4

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.079

Sift

Benign

0.37

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.083

MPC

0.14

ClinPred

0.010

GERP RS

-6.7

PromoterAI

0.050

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.30

gMVP

0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over