Variant rs3129888 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019111.5(HLA-DRA):c.*11+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 1,491,692 control chromosomes in the GnomAD database, including 497,078 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 0.81 ( 50032 hom., cov: 31)

Exomes 𝑓: 0.82 ( 447046 hom. )

Consequence

HLA-DRA
NM_019111.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.717

Variant links:

Genes affected

HLA-DRA (HGNC:4947): (major histocompatibility complex, class II, DR alpha) HLA-DRA is one of the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha and a beta chain, both anchored in the membrane. This molecule is expressed on the surface of various antigen presenting cells such as B lymphocytes, dendritic cells, and monocytes/macrophages, and plays a central role in the immune system and response by presenting peptides derived from extracellular proteins, in particular, pathogen-derived peptides to T cells. The alpha chain is approximately 33-35 kDa and its gene contains 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. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5. [provided by RefSeq, Aug 2020]

HLA-DRA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DRA	NM_019111.5 link	c.*11+28G>A		intron_variant		ENST00000395388.7	NP_061984.2	P01903A0A0G2JMH6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DRA	ENST00000395388.7 link	c.*11+28G>A		intron_variant		6	NM_019111.5	ENSP00000378786.2		P01903
HLA-DRA	ENST00000374982.5 link	c.*11+28G>A		intron_variant		6		ENSP00000364121.5		Q30118

Frequencies

GnomAD3 genomes

AF:

0.809

AC:

123004

AN:

152000

Hom.:

50015

Cov.:

show subpopulations

Gnomad AFR

AF:

0.793

Gnomad AMI

AF:

0.898

Gnomad AMR

AF:

0.822

Gnomad ASJ

AF:

0.909

Gnomad EAS

AF:

0.965

Gnomad SAS

AF:

0.965

Gnomad FIN

AF:

0.724

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.799

Gnomad OTH

AF:

0.842

GnomAD3 exomes

AF:

0.821

AC:

145373

AN:

176966

Hom.:

60226

AF XY:

0.830

AC XY:

79544

AN XY:

95828

show subpopulations

Gnomad AFR exome

AF:

0.788

Gnomad AMR exome

AF:

0.777

Gnomad ASJ exome

AF:

0.901

Gnomad EAS exome

AF:

0.967

Gnomad SAS exome

AF:

0.962

Gnomad FIN exome

AF:

0.724

Gnomad NFE exome

AF:

0.803

Gnomad OTH exome

AF:

0.816

GnomAD4 exome

AF:

0.816

AC:

1092463

AN:

1339574

Hom.:

447046

Cov.:

AF XY:

0.819

AC XY:

538708

AN XY:

657588

show subpopulations

Gnomad4 AFR exome

AF:

0.794

Gnomad4 AMR exome

AF:

0.791

Gnomad4 ASJ exome

AF:

0.901

Gnomad4 EAS exome

AF:

0.952

Gnomad4 SAS exome

AF:

0.961

Gnomad4 FIN exome

AF:

0.728

Gnomad4 NFE exome

AF:

0.805

Gnomad4 OTH exome

AF:

0.822

GnomAD4 genome

AF:

0.809

AC:

123073

AN:

152118

Hom.:

50032

Cov.:

AF XY:

0.809

AC XY:

60114

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.793

Gnomad4 AMR

AF:

0.822

Gnomad4 ASJ

AF:

0.909

Gnomad4 EAS

AF:

0.964

Gnomad4 SAS

AF:

0.965

Gnomad4 FIN

AF:

0.724

Gnomad4 NFE

AF:

0.799

Gnomad4 OTH

AF:

0.843

Alfa

AF:

0.820

Hom.:

72488

Bravo

AF:

0.814

Asia WGS

AF:

0.927

AC:

3224

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.47

DANN

Benign

0.61

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