rs41270488

Variant summary

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

The NM_019111.5(HLA-DRA):​c.82+97T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 1,048,576 control chromosomes in the GnomAD database, including 3,924 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 0.061 ( 478 hom., cov: 30)
Exomes 𝑓: 0.075 ( 3446 hom. )

Consequence

HLA-DRA
NM_019111.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.97
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HLA-DRANM_019111.5 linkuse as main transcriptc.82+97T>C intron_variant ENST00000395388.7 NP_061984.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HLA-DRAENST00000395388.7 linkuse as main transcriptc.82+97T>C intron_variant NM_019111.5 ENSP00000378786 P1
HLA-DRAENST00000374982.5 linkuse as main transcriptc.82+97T>C intron_variant ENSP00000364121

Frequencies

GnomAD3 genomes
AF:
0.0613
AC:
9322
AN:
152052
Hom.:
478
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0129
Gnomad AMI
AF:
0.108
Gnomad AMR
AF:
0.0743
Gnomad ASJ
AF:
0.132
Gnomad EAS
AF:
0.00289
Gnomad SAS
AF:
0.0433
Gnomad FIN
AF:
0.0397
Gnomad MID
AF:
0.150
Gnomad NFE
AF:
0.0921
Gnomad OTH
AF:
0.0672
GnomAD4 exome
AF:
0.0751
AC:
67296
AN:
896406
Hom.:
3446
AF XY:
0.0769
AC XY:
35731
AN XY:
464648
show subpopulations
Gnomad4 AFR exome
AF:
0.0111
Gnomad4 AMR exome
AF:
0.0529
Gnomad4 ASJ exome
AF:
0.144
Gnomad4 EAS exome
AF:
0.00114
Gnomad4 SAS exome
AF:
0.0576
Gnomad4 FIN exome
AF:
0.0426
Gnomad4 NFE exome
AF:
0.0853
Gnomad4 OTH exome
AF:
0.0761
GnomAD4 genome
AF:
0.0612
AC:
9317
AN:
152170
Hom.:
478
Cov.:
30
AF XY:
0.0590
AC XY:
4393
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.0129
Gnomad4 AMR
AF:
0.0742
Gnomad4 ASJ
AF:
0.132
Gnomad4 EAS
AF:
0.00290
Gnomad4 SAS
AF:
0.0431
Gnomad4 FIN
AF:
0.0397
Gnomad4 NFE
AF:
0.0921
Gnomad4 OTH
AF:
0.0665
Alfa
AF:
0.0858
Hom.:
162
Bravo
AF:
0.0604
Asia WGS
AF:
0.0180
AC:
63
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
11
DANN
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs41270488; hg19: chr6-32407906; API