rs6914849

Variant names:

• chr6-33072938-G-A
• rs6914849
• ENST00000692443.1:c.100+533C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33072938-G-A
• chr6-33072938-G-C
• chr6-33072938-G-T

Variant summary

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

The ENST00000692443.1(HLA-DPA1):​c.100+533C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,938 control chromosomes in the GnomAD database, including 8,092 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 0.29 (8092 hom., cov: 32)
• Consequence: HLA-DPA1 ENST00000692443.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 18 publications found

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]

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 (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPA1	NM_001242524.2	c.100+533C>T		intron_variant	Intron 2 of 5		NP_001229453.1
HLA-DPA1	NM_001242525.2	c.100+533C>T		intron_variant	Intron 2 of 5		NP_001229454.1
HLA-DPA1	NM_001405020.1	c.100+533C>T		intron_variant	Intron 1 of 3		NP_001391949.1
HLA-DPA1	NM_033554.4	c.100+533C>T		intron_variant	Intron 1 of 4		NP_291032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPA1	ENST00000692443.1	c.100+533C>T		intron_variant	Intron 1 of 4			ENSP00000509163.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43290 AN: 151820 Hom.: 8076 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.285 AC: 43334 AN: 151938 Hom.: 8092 Cov.: 32 AF XY: 0.282 AC XY: 20970 AN XY: 74282

African (AFR) AF: 0.485 AC: 20061 AN: 41324

American (AMR) AF: 0.244 AC: 3730 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3472

East Asian (EAS) AF: 0.661 AC: 3416 AN: 5166

South Asian (SAS) AF: 0.334 AC: 1613 AN: 4824

European-Finnish (FIN) AF: 0.102 AC: 1083 AN: 10596

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12017 AN: 67962

Other (OTH) AF: 0.307 AC: 647 AN: 2106

Alfa AF: 0.238 Hom.: 6635

Bravo AF: 0.304

Asia WGS AF: 0.432 AC: 1503 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	1.6
DANN	Benign	0.50
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6914849; hg19: chr6-33040715;