rs6914849

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242525.2(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 NM_001242525.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HLA-DPA1	NM_033554.4	c.100+533C>T		intron_variant		ENST00000692443.1
HLA-DPA1	NM_001242525.2	c.100+533C>T		intron_variant
HLA-DPA1	NM_001242524.2	c.100+533C>T		intron_variant
HLA-DPA1	NM_001405020.1	c.100+533C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DPA1	ENST00000692443.1	c.100+533C>T		intron_variant			NM_033554.4	P1

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

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.307

Alfa AF: 0.194 Hom.: 1850

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6914849; hg19: chr6-33040715;