6-33068400-A-G

Variant names:

• chr6-33068400-A-G
• rs3180554
• NM_033554.4:c.*12+238T>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.*12+238T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 433,916 control chromosomes in the GnomAD database, including 20,149 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 0.32 (10914 hom., cov: 32)
  • Exomes 𝑓: 0.21 (9235 hom.)
• Consequence: HLA-DPA1 NM_033554.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452
• Publications: 4 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 = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPA1	NM_033554.4	c.*12+238T>C		intron_variant	Intron 4 of 4	ENST00000692443.1	NP_291032.2
HLA-DPA1	NM_001405020.1	c.*250T>C		3_prime_UTR_variant	Exon 4 of 4		NP_001391949.1
HLA-DPA1	NM_001242524.2	c.*12+238T>C		intron_variant	Intron 5 of 5		NP_001229453.1
HLA-DPA1	NM_001242525.2	c.*12+238T>C		intron_variant	Intron 5 of 5		NP_001229454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPA1	ENST00000692443.1	c.*12+238T>C		intron_variant	Intron 4 of 4		NM_033554.4	ENSP00000509163.1
HLA-DPA1	ENST00000479107.1	n.1632T>C		non_coding_transcript_exon_variant	Exon 2 of 2	6
HLA-DPA1	ENST00000437811.1	c.*250T>C		3_prime_UTR_variant	Exon 2 of 2	6		ENSP00000405500.1
HLA-DPA1	ENST00000419277.5	c.*12+238T>C		intron_variant	Intron 5 of 5	6		ENSP00000393566.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48587 AN: 151950 Hom.: 10866 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.207 AC: 58319 AN: 281848 Hom.: 9235 Cov.: 2 AF XY: 0.206 AC XY: 29599 AN XY: 143944

African (AFR) AF: 0.577 AC: 4308 AN: 7466

American (AMR) AF: 0.221 AC: 2282 AN: 10304

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 1737 AN: 10004

East Asian (EAS) AF: 0.596 AC: 12511 AN: 20982

South Asian (SAS) AF: 0.248 AC: 2972 AN: 11998

European-Finnish (FIN) AF: 0.0790 AC: 1929 AN: 24432

Middle Eastern (MID) AF: 0.166 AC: 235 AN: 1412

European-Non Finnish (NFE) AF: 0.158 AC: 28088 AN: 177372

Other (OTH) AF: 0.238 AC: 4257 AN: 17878

GnomAD4 genome AF: 0.320 AC: 48693 AN: 152068 Hom.: 10914 Cov.: 32 AF XY: 0.317 AC XY: 23575 AN XY: 74362

African (AFR) AF: 0.600 AC: 24872 AN: 41422

American (AMR) AF: 0.260 AC: 3971 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3462

East Asian (EAS) AF: 0.688 AC: 3553 AN: 5164

South Asian (SAS) AF: 0.343 AC: 1655 AN: 4822

European-Finnish (FIN) AF: 0.103 AC: 1089 AN: 10614

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

European-Non Finnish (NFE) AF: 0.177 AC: 12023 AN: 67992

Other (OTH) AF: 0.336 AC: 709 AN: 2110

Alfa AF: 0.240 Hom.: 2580

Bravo AF: 0.344

Asia WGS AF: 0.462 AC: 1605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.9
DANN	Benign	0.61
PhyloP100		-0.45
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: rs3180554; hg19: chr6-33036177;