Variant rs375256 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002119.4(HLA-DOA):c.252C>T(p.Gly84Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,612,792 control chromosomes in the GnomAD database, including 47,458 homozygotes. 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 0.20 ( 3711 hom., cov: 33)

Exomes 𝑓: 0.24 ( 43747 hom. )

Consequence

HLA-DOA
NM_002119.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.92

Variant links:

Genes affected

HLA-DOA (HGNC:4936): (major histocompatibility complex, class II, DO alpha) HLA-DOA belongs to the HLA class II alpha chain paralogues. HLA-DOA forms a heterodimer with HLA-DOB. The heterodimer, HLA-DO, is found in lysosomes in B cells and regulates HLA-DM-mediated peptide loading on MHC class II molecules. In comparison with classical HLA class II molecules, this gene exhibits very little sequence variation, especially at the protein level. [provided by RefSeq, Jul 2008]

HLA-DOA links:

HLA-DOA (HGNC:):

HLA-DOA 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 (MetaRNN=0.0011001527).

BP7

Synonymous conserved (PhyloP=-3.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DOA	NM_002119.4 linkuse as main transcript	c.252C>T	p.Gly84Gly	synonymous_variant	2/5	ENST00000229829.7	NP_002110.1	P06340X5CF87A0A1V0E3Q8A0A1V0E3Q5A0A1V0E3N1A0A1V0E3M7A0A1V0E3R3A0A1V0E3S6A0A1V0E3T1A0A1V0E3P8A0A1V0E3Q2A0A1V0E3P6A0A1V0E3S7A0A1V0E3P1A0A1V0E3Q6A0A1V0E3P3A0A1V0E3R6A0A1V0E3P9A0A1V0E3N7A0A1V0E3S0A0A1V0E3Q1A0A1V0E3N3A0A1V0E3Q4A0A1V0E3R4A0A1V0E3P0A0A1V0E3R0A0A1V0E3N6A0A1V0E3R8A0A1V0E3S4A0A1V0E3Q7A0A1V0E3Q3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DOA	ENST00000229829.7 linkuse as main transcript	c.252C>T	p.Gly84Gly	synonymous_variant	2/5	6	NM_002119.4	ENSP00000229829.3		P06340

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31031

AN:

152052

Hom.:

3704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0997

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.386

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.171

GnomAD3 exomes

AF:

0.229

AC:

56426

AN:

246120

Hom.:

7459

AF XY:

0.233

AC XY:

31241

AN XY:

134208

show subpopulations

Gnomad AFR exome

AF:

0.0950

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.0995

Gnomad EAS exome

AF:

0.417

Gnomad SAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.261

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.240

AC:

350241

AN:

1460622

Hom.:

43747

Cov.:

AF XY:

0.239

AC XY:

173799

AN XY:

726624

show subpopulations

Gnomad4 AFR exome

AF:

0.0973

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.325

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.280

Gnomad4 NFE exome

AF:

0.252

Gnomad4 OTH exome

AF:

0.224

GnomAD4 genome

AF:

0.204

AC:

31063

AN:

152170

Hom.:

3711

Cov.:

AF XY:

0.206

AC XY:

15311

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.100

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.387

Gnomad4 SAS

AF:

0.187

Gnomad4 FIN

AF:

0.280

Gnomad4 NFE

AF:

0.256

Gnomad4 OTH

AF:

0.175

Alfa

AF:

0.209

Hom.:

2179

Bravo

AF:

0.192

TwinsUK

AF:

0.252

AC:

934

ALSPAC

AF:

0.245

AC:

943

ESP6500AA

AF:

0.101

AC:

306

ESP6500EA

AF:

0.255

AC:

1384

ExAC

AF:

0.234

AC:

27538

Asia WGS

AF:

0.229

AC:

797

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.20

DANN

Benign

0.62

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0082

MetaRNN

Benign

0.0011

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.17

REVEL

Benign

0.013

Sift

Benign

0.047

ClinPred

0.020

GERP RS

-9.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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