Variant 6-33069898-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001242525.2(HLA-DPA1):c.101-12G>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,557,554 control chromosomes in the GnomAD database, including 49,872 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 0.32 ( 11147 hom., cov: 32)

Exomes 𝑓: 0.19 ( 38725 hom. )

Consequence

HLA-DPA1
NM_001242525.2 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004156

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.274

Variant links:

Genes affected

HLA-DPA1 (HGNC:4938): (major histocompatibility complex, class II, DP alpha 1) HLA-DPA1 belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta (DPB) chain, 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 and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules. [provided by RefSeq, Jul 2008]

HLA-DPA1 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=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
HLA-DPA1	NM_033554.4 linkuse as main transcript	c.101-12G>T	splice_polypyrimidine_tract_variant, intron_variant	ENST00000692443.1	NP_291032.2
HLA-DPA1	NM_001242525.2 linkuse as main transcript	c.101-12G>T	splice_polypyrimidine_tract_variant, intron_variant		NP_001229454.1
HLA-DPA1	NM_001242524.2 linkuse as main transcript	c.101-12G>T	splice_polypyrimidine_tract_variant, intron_variant		NP_001229453.1
HLA-DPA1	NM_001405020.1 linkuse as main transcript	c.101-12G>T	splice_polypyrimidine_tract_variant, intron_variant		NP_001391949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DPA1	ENST00000692443.1 linkuse as main transcript	c.101-12G>T		splice_polypyrimidine_tract_variant, intron_variant			NM_033554.4	ENSP00000509163	P1

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48939

AN:

151828

Hom.:

11100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.610

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.260

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.687

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.329

GnomAD3 exomes

AF:

0.232

AC:

53652

AN:

231370

Hom.:

10641

AF XY:

0.228

AC XY:

28705

AN XY:

126042

show subpopulations

Gnomad AFR exome

AF:

0.628

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.686

Gnomad SAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.0930

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.195

AC:

273453

AN:

1405608

Hom.:

38725

Cov.:

AF XY:

0.197

AC XY:

137206

AN XY:

698164

show subpopulations

Gnomad4 AFR exome

AF:

0.630

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.177

Gnomad4 EAS exome

AF:

0.631

Gnomad4 SAS exome

AF:

0.298

Gnomad4 FIN exome

AF:

0.0991

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.228

GnomAD4 genome

AF:

0.323

AC:

49044

AN:

151946

Hom.:

11147

Cov.:

AF XY:

0.320

AC XY:

23752

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.611

Gnomad4 AMR

AF:

0.260

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.688

Gnomad4 SAS

AF:

0.344

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.335

Alfa

AF:

0.210

Hom.:

7167

Bravo

AF:

0.346

Asia WGS

AF:

0.463

AC:

1608

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.2

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000042

dbscSNV1_RF

Benign

0.034

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