rs3135394

Variant names:

• chr6-32440720-A-G
• rs3135394
• NM_019111.5:c.82+688A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-32440720-A-G
• chr6-32440720-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019111.5(HLA-DRA):​c.82+688A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0622 in 152,274 control chromosomes in the GnomAD database, including 452 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 0.062 (452 hom., cov: 32)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 47 publications found

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]

ENSG00000299747 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DRA	NM_019111.5	c.82+688A>G		intron_variant	Intron 1 of 4	ENST00000395388.7	NP_061984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DRA	ENST00000395388.7	c.82+688A>G		intron_variant	Intron 1 of 4	6	NM_019111.5	ENSP00000378786.2
HLA-DRA	ENST00000374982.5	c.82+688A>G		intron_variant	Intron 1 of 4	6		ENSP00000364121.5
ENSG00000299747	ENST00000766007.1	n.163-2460T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0622 AC: 9470 AN: 152156 Hom.: 452 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.0384

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0478

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0622 AC: 9467 AN: 152274 Hom.: 452 Cov.: 32 AF XY: 0.0578 AC XY: 4302 AN XY: 74468

African (AFR) AF: 0.0160 AC: 664 AN: 41560

American (AMR) AF: 0.0281 AC: 430 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0384 AC: 133 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.0837 AC: 889 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7193 AN: 68006

Other (OTH) AF: 0.0473 AC: 100 AN: 2116

Alfa AF: 0.101 Hom.: 2611

Bravo AF: 0.0567

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.0
DANN	Benign	0.75
PhyloP100		0.085
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3135394; hg19: chr6-32408497;