Variant 6-33007564-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002119.4(HLA-DOA):c.360G>A(p.Lys120=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00613 in 1,612,550 control chromosomes in the GnomAD database, including 534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.031 ( 242 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 292 hom. )

Consequence

HLA-DOA
NM_002119.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.471

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015556812).

BP6

Variant 6-33007564-C-T is Benign according to our data. Variant chr6-33007564-C-T is described in ClinVar as [Benign]. Clinvar id is 792038.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.471 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 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.360G>A	p.Lys120=	synonymous_variant	3/5	ENST00000229829.7	NP_002110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	Appris
HLA-DOA	ENST00000229829.7 linkuse as main transcript	c.360G>A	p.Lys120=	synonymous_variant	3/5	NM_002119.4	ENSP00000229829	P1
HLA-DOA	ENST00000374813.1 linkuse as main transcript	c.193G>A	p.Val65Ile	missense_variant	3/3		ENSP00000363946
HLA-DOA	ENST00000485901.1 linkuse as main transcript	n.71G>A		non_coding_transcript_exon_variant	2/3
HLA-DOA	ENST00000495532.1 linkuse as main transcript	n.426G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0312

AC:

4743

AN:

152156

Hom.:

241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0192

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0344

GnomAD3 exomes

AF:

0.00798

AC:

1959

AN:

245516

Hom.:

AF XY:

0.00597

AC XY:

799

AN XY:

133830

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.00547

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000957

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000173

Gnomad OTH exome

AF:

0.00447

GnomAD4 exome

AF:

0.00351

AC:

5129

AN:

1460276

Hom.:

292

Cov.:

AF XY:

0.00302

AC XY:

2192

AN XY:

726418

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.00692

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000986

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000729

Gnomad4 OTH exome

AF:

0.00776

GnomAD4 genome

AF:

0.0312

AC:

4758

AN:

152274

Hom.:

242

Cov.:

AF XY:

0.0304

AC XY:

2266

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.0192

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0341

Alfa

AF:

0.00860

Hom.:

Bravo

AF:

0.0374

ESP6500AA

AF:

0.116

AC:

351

ESP6500EA

AF:

0.000369

AC:

ExAC

AF:

0.00952

AC:

1124

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

0.054

Eigen_PC

Benign

0.046

FATHMM_MKL

Benign

0.18

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.81

MutationTaster

Benign

4.6e-10

P;P

PROVEAN

Benign

-0.17

REVEL

Benign

0.063

Sift

Pathogenic

0.0

MVP

0.088

ClinPred

0.038

GERP RS

4.5

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over