6-33065245-A-G

Variant names:

• chr6-33065245-A-G
• rs3077
• NM_033554.4:c.*115T>C

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.*115T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,222 control chromosomes in the GnomAD database, including 8,455 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 (8455 hom., cov: 32)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: HLA-DPA1 NM_033554.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 209 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 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.*115T>C		3_prime_UTR	Exon 5 of 5	NP_291032.2
	HLA-DPA1	NM_001242524.2		c.*115T>C		3_prime_UTR	Exon 6 of 6	NP_001229453.1
	HLA-DPA1	NM_001242525.2		c.*115T>C		3_prime_UTR	Exon 6 of 6	NP_001229454.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DPA1	ENST00000692443.1	MANE Select	c.*115T>C		3_prime_UTR	Exon 5 of 5	ENSP00000509163.1
	HLA-DPA1	ENST00000479107.1	TSL:6	n.4787T>C		non_coding_transcript_exon	Exon 2 of 2
	HLA-DPA1	ENST00000419277.5	TSL:6	c.*115T>C		3_prime_UTR	Exon 6 of 6	ENSP00000393566.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44035 AN: 151970 Hom.: 8436 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.119 AC: 16 AN: 134 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 12 AN XY: 96

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.121 AC: 14 AN: 116

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.290 AC: 44085 AN: 152088 Hom.: 8455 Cov.: 32 AF XY: 0.287 AC XY: 21366 AN XY: 74358

African (AFR) AF: 0.497 AC: 20603 AN: 41442

American (AMR) AF: 0.246 AC: 3762 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3472

East Asian (EAS) AF: 0.689 AC: 3561 AN: 5166

South Asian (SAS) AF: 0.343 AC: 1652 AN: 4820

European-Finnish (FIN) AF: 0.103 AC: 1089 AN: 10592

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11997 AN: 67986

Other (OTH) AF: 0.309 AC: 651 AN: 2110

Alfa AF: 0.219 Hom.: 19288

Bravo AF: 0.308

Asia WGS AF: 0.452 AC: 1570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.56
PhyloP100		-0.21
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: rs3077; hg19: chr6-33033022;