rs3129882

Variant names:

• chr6-32441753-G-A
• rs3129882
• NM_019111.5:c.83-695G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-32441753-G-A
• chr6-32441753-G-C

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The NM_019111.5(HLA-DRA):c.83-695G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.553 (AC=84,019) in the gnomAD database across 151,994 control chromosomes, including 23,495 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.561. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23495 hom., cov: 31)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 1 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:):

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.561 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_019111.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	HLA-DRA NM_019111.5	MANE Select	c.83-695G>A	intron	Intron 1 of 4	Prot: NP_061984.2

HLA-DRA NM_019111.5

MANE Select

HGVSc / HGVSpc.83-695G>A

Exon rankIntron 1 of 4

intron

Prot: NP_061984.2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	HLA-DRA ENST00000395388.7	TSL:6MANE Select	c.83-695G>A	intron	Intron 1 of 4	Prot: ENSP00000378786.2 UniProt:
	HLA-DRA ENST00000870696.1		c.83-695G>A	intron	Intron 1 of 3	Prot: ENSP00000540755.1 UniProt:
	HLA-DRA ENST00000917299.1		c.83-695G>A	intron	Intron 1 of 4	Prot: ENSP00000587358.1 UniProt:

HLA-DRA ENST00000395388.7

TSL:6MANE Select

HGVSc / HGVSpc.83-695G>A

Exon rankIntron 1 of 4

intron

Prot: ENSP00000378786.2UniProt: P01903

HLA-DRA ENST00000870696.1

HGVSc / HGVSpc.83-695G>A

Exon rankIntron 1 of 3

intron

Prot: ENSP00000540755.1UniProt: P01903

HLA-DRA ENST00000917299.1

HGVSc / HGVSpc.83-695G>A

Exon rankIntron 1 of 4

intron

Prot: ENSP00000587358.1UniProt: P01903

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.553	AC:83971	Hom:23481	AN:151876	Cov:31
GnomAD4 genome	AF: 0.553	AC:84019	Hom:23495	AN:151994	Cov:31
TOPMed (Bravo)	AF: 0.557	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.565	AC:402298	Hom:114906	AN:712332	Cov:
Local & regional cohorts 9 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.541	AC:1268	Hom:346	AN:2342	Cov:
Denmark Genome	AF: 0.610	AC:183	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.425	AC:1484	Hom:	AN:3476	Cov:
Korea4K (4,157 Koreans)	AF: 0.521	AC:3768	Hom:	AN:7232	Cov:
Qatari Genome	AF: 0.563	AC:99	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.438	AC:53685	Hom:11836	AN:122644	Cov:
Turkish Variome	AF: 0.445	AC:688	Hom:159	AN:1546	Cov:
UK10K	AF: 0.612	AC:4630	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.376	AC:3369	Hom:646	AN:8960	Cov:

Showing 13 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	7.7
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.54
GPN-Star LLR	N/A	5.3
GPN-Star score	N/A	1.2
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	1.5

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs3129882;

hg19: chr6-32409530;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar