6-33070989-C-T

Variant names:

• chr6-33070989-C-T
• rs2301220
• NM_033554.4:c.101-1103G>A

Variant summary

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

The NM_033554.4(HLA-DPA1):​c.101-1103G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,986 control chromosomes in the GnomAD database, including 8,137 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 (8137 hom., cov: 32)
• Consequence: HLA-DPA1 NM_033554.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 35 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033554.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DPA1	NM_033554.4	MANE Select	c.101-1103G>A		intron	N/A	NP_291032.2
	HLA-DPA1	NM_001242524.2		c.101-1103G>A		intron	N/A	NP_001229453.1
	HLA-DPA1	NM_001242525.2		c.101-1103G>A		intron	N/A	NP_001229454.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DPA1	ENST00000692443.1	MANE Select	c.101-1103G>A		intron	N/A	ENSP00000509163.1
	HLA-DPA1	ENST00000419277.5	TSL:6	c.101-1103G>A		intron	N/A	ENSP00000393566.1
	HLA-DPA1	ENST00000453337.1	TSL:6	c.101-1103G>A		intron	N/A	ENSP00000390929.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43393 AN: 151866 Hom.: 8121 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.103

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: 0.286 AC: 43437 AN: 151986 Hom.: 8137 Cov.: 32 AF XY: 0.283 AC XY: 21025 AN XY: 74302

African (AFR) AF: 0.486 AC: 20135 AN: 41406

American (AMR) AF: 0.244 AC: 3729 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3468

East Asian (EAS) AF: 0.663 AC: 3429 AN: 5174

South Asian (SAS) AF: 0.335 AC: 1614 AN: 4822

European-Finnish (FIN) AF: 0.103 AC: 1087 AN: 10576

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

European-Non Finnish (NFE) AF: 0.177 AC: 12032 AN: 67960

Other (OTH) AF: 0.307 AC: 646 AN: 2102

Alfa AF: 0.229 Hom.: 9574

Bravo AF: 0.304

Asia WGS AF: 0.432 AC: 1503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.57
PhyloP100		-0.48
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: rs2301220; hg19: chr6-33038766;