dbSNP rs7195: HLA-DRA:c.*122A>G (chr6-32444762-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019111.5(HLA-DRA):c.*122A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,282 control chromosomes in the GnomAD database, including 29,319 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 0.62 ( 29237 hom., cov: 31)

Exomes 𝑓: 0.81 ( 82 hom. )

Consequence

HLA-DRA
NM_019111.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.204

Publications

43 publications found

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:

ENSG00000299747 (HGNC:):

ENSG00000299747 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DRA	NM_019111.5 link	c.*122A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000395388.7	NP_061984.2	P01903A0A0G2JMH6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HLA-DRA	ENST00000395388.7 link	c.*122A>G	3_prime_UTR_variant	Exon 5 of 5	6	NM_019111.5	ENSP00000378786.2	P01903
HLA-DRA	ENST00000374982.5 link	c.*122A>G	3_prime_UTR_variant	Exon 5 of 5	6		ENSP00000364121.5	Q30118
ENSG00000299747	ENST00000766007.1 link	n.163-6502T>C	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.616

AC:

93623

AN:

151912

Hom.:

29218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.598

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.671

Gnomad ASJ

AF:

0.747

Gnomad EAS

AF:

0.707

Gnomad SAS

AF:

0.741

Gnomad FIN

AF:

0.518

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.604

Gnomad OTH

AF:

0.651

GnomAD4 exome

AF:

0.806

AC:

203

AN:

252

Hom.:

Cov.:

AF XY:

0.779

AC XY:

106

AN XY:

136

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.833

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.813

AC:

161

AN:

198

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AF:

0.688

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.543

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.616

AC:

93685

AN:

152030

Hom.:

29237

Cov.:

AF XY:

0.618

AC XY:

45908

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.597

AC:

24767

AN:

41474

American (AMR)

AF:

0.671

AC:

10251

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.747

AC:

2591

AN:

3470

East Asian (EAS)

AF:

0.707

AC:

3647

AN:

5158

South Asian (SAS)

AF:

0.742

AC:

3581

AN:

4824

European-Finnish (FIN)

AF:

0.518

AC:

5466

AN:

10558

Middle Eastern (MID)

AF:

0.721

AC:

212

AN:

294

European-Non Finnish (NFE)

AF:

0.605

AC:

41082

AN:

67956

Other (OTH)

AF:

0.653

AC:

1376

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1790

3580

5369

7159

8949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.611

Hom.:

107214

Bravo

AF:

0.627

Asia WGS

AF:

0.693

AC:

2411

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

4.7

(source)

DANN

Benign

0.46

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over