Variant rs707949 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002122.5(HLA-DQA1):c.535T>C(p.Phe179Leu) variant causes a missense 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 0.017 ( 12 hom., cov: 16)

Exomes 𝑓: 0.095 ( 17132 hom. )

Failed GnomAD Quality Control

Consequence

HLA-DQA1
NM_002122.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.18

Variant links:

Genes affected

HLA-DQA1 (HGNC:4942): (major histocompatibility complex, class II, DQ alpha 1) HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B Lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. [provided by RefSeq, Jul 2008]

HLA-DQA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016901493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5 linkuse as main transcript	c.535T>C	p.Phe179Leu	missense_variant	3/5	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5 linkuse as main transcript	c.535T>C	p.Phe179Leu	missense_variant	3/4		XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11 linkuse as main transcript	c.535T>C	p.Phe179Leu	missense_variant	3/5		NM_002122.5	ENSP00000339398	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1478

AN:

89304

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0135

Gnomad AMI

AF:

0.00680

Gnomad AMR

AF:

0.0167

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.00830

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.00748

Gnomad MID

AF:

0.00806

Gnomad NFE

AF:

0.0207

Gnomad OTH

AF:

0.0106

GnomAD3 exomes

AF:

0.177

AC:

36739

AN:

207616

Hom.:

6718

AF XY:

0.180

AC XY:

20250

AN XY:

112360

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.216

Gnomad ASJ exome

AF:

0.255

Gnomad EAS exome

AF:

0.129

Gnomad SAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.178

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0947

AC:

105146

AN:

1109920

Hom.:

17132

Cov.:

AF XY:

0.0993

AC XY:

55081

AN XY:

554592

show subpopulations

Gnomad4 AFR exome

AF:

0.0690

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.158

Gnomad4 EAS exome

AF:

0.0550

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.0602

Gnomad4 NFE exome

AF:

0.0887

Gnomad4 OTH exome

AF:

0.0945

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0166

AC:

1480

AN:

89396

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

660

AN XY:

43640

show subpopulations

Gnomad4 AFR

AF:

0.0135

Gnomad4 AMR

AF:

0.0167

Gnomad4 ASJ

AF:

0.0251

Gnomad4 EAS

AF:

0.00832

Gnomad4 SAS

AF:

0.0148

Gnomad4 FIN

AF:

0.00748

Gnomad4 NFE

AF:

0.0207

Gnomad4 OTH

AF:

0.0105

Alfa

AF:

0.199

Hom.:

773

ExAC

AF:

0.209

AC:

24496

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

.;.;T;.

Eigen

Benign

0.022

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.78

.;.;T;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.00040

P;P;P;P

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.0

D;D;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.025

D;D;D;D

Sift4G

Benign

0.068

T;T;T;T

Vest4

0.28

MutPred

0.87

Gain of catalytic residue at F179 (P = 0.052);Gain of catalytic residue at F179 (P = 0.052);Gain of catalytic residue at F179 (P = 0.052);Gain of catalytic residue at F179 (P = 0.052);

MPC

1.1

ClinPred

0.040

GERP RS

4.1

gMVP

0.87

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