chr6-33069410-C-G

Variant names:

• chr6-33069410-C-G
• rs3830066
• NM_033554.4:c.347-110G>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.347-110G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,158,104 control chromosomes in the GnomAD database, including 29,791 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 (8535 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21256 hom.)
• Consequence: HLA-DPA1 NM_033554.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274
• Publications: 12 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPA1	NM_033554.4	c.347-110G>C		intron_variant	Intron 2 of 4	ENST00000692443.1	NP_291032.2
HLA-DPA1	NM_001242524.2	c.347-110G>C		intron_variant	Intron 3 of 5		NP_001229453.1
HLA-DPA1	NM_001242525.2	c.347-110G>C		intron_variant	Intron 3 of 5		NP_001229454.1
HLA-DPA1	NM_001405020.1	c.347-110G>C		intron_variant	Intron 2 of 3		NP_001391949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPA1	ENST00000692443.1	c.347-110G>C		intron_variant	Intron 2 of 4		NM_033554.4	ENSP00000509163.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44297 AN: 151918 Hom.: 8516 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.170 AC: 170691 AN: 1006066 Hom.: 21256 Cov.: 14 AF XY: 0.175 AC XY: 88767 AN XY: 507092

African (AFR) AF: 0.456 AC: 9278 AN: 20352

American (AMR) AF: 0.175 AC: 5236 AN: 30002

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 2897 AN: 18222

East Asian (EAS) AF: 0.624 AC: 22204 AN: 35594

South Asian (SAS) AF: 0.299 AC: 18489 AN: 61916

European-Finnish (FIN) AF: 0.103 AC: 4942 AN: 48006

Middle Eastern (MID) AF: 0.195 AC: 871 AN: 4470

European-Non Finnish (NFE) AF: 0.132 AC: 97983 AN: 743580

Other (OTH) AF: 0.200 AC: 8791 AN: 43924

GnomAD4 genome AF: 0.292 AC: 44348 AN: 152038 Hom.: 8535 Cov.: 32 AF XY: 0.289 AC XY: 21486 AN XY: 74316

African (AFR) AF: 0.497 AC: 20593 AN: 41416

American (AMR) AF: 0.248 AC: 3787 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 589 AN: 3472

East Asian (EAS) AF: 0.691 AC: 3573 AN: 5168

South Asian (SAS) AF: 0.349 AC: 1679 AN: 4810

European-Finnish (FIN) AF: 0.104 AC: 1100 AN: 10610

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.179 AC: 12180 AN: 67960

Other (OTH) AF: 0.313 AC: 660 AN: 2112

Alfa AF: 0.0859 Hom.: 109

Bravo AF: 0.310

Asia WGS AF: 0.460 AC: 1597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.5
DANN	Benign	0.72
PhyloP100		0.27
PromoterAI		-0.0036	Neutral
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: rs3830066; hg19: chr6-33037187;