ENST00000454398.1:n.103-1887C>T

Variant names:

• chr6-33133229-G-A
• rs2395357
• ENST00000454398.1:n.103-1887C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000454398.1(HLA-DPA3):​n.103-1887C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 152,220 control chromosomes in the GnomAD database, including 152 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 0.034 (152 hom., cov: 32)
• Consequence: HLA-DPA3 ENST00000454398.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 4 publications found

Genes affected

HLA-DPA3 (HGNC:19393): (major histocompatibility complex, class II, DP alpha 3 (pseudogene))

ENSG00000291111 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.034 (5173/152220) while in subpopulation SAS AF = 0.0537 (258/4808). AF 95% confidence interval is 0.0483. There are 152 homozygotes in GnomAd4. There are 2470 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 152 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375021	NR_190905.1	n.492+851C>T		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPA3	ENST00000454398.1	n.103-1887C>T		intron_variant	Intron 1 of 1	6
ENSG00000291111	ENST00000782892.1	n.430-7892G>A		intron_variant	Intron 2 of 2
ENSG00000291111	ENST00000782893.1	n.404-7892G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 5171 AN: 152102 Hom.: 153 Cov.: 32

Gnomad AFR AF: 0.00927

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0337

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.0538

Gnomad FIN AF: 0.0259

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0443

Gnomad OTH AF: 0.0435

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0340 AC: 5173 AN: 152220 Hom.: 152 Cov.: 32 AF XY: 0.0332 AC XY: 2470 AN XY: 74436

African (AFR) AF: 0.00944 AC: 392 AN: 41538

American (AMR) AF: 0.0336 AC: 514 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 508 AN: 3470

East Asian (EAS) AF: 0.0178 AC: 92 AN: 5178

South Asian (SAS) AF: 0.0537 AC: 258 AN: 4808

European-Finnish (FIN) AF: 0.0259 AC: 275 AN: 10604

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0443 AC: 3013 AN: 68010

Other (OTH) AF: 0.0421 AC: 89 AN: 2114

Alfa AF: 0.0249 Hom.: 20

Bravo AF: 0.0318

Asia WGS AF: 0.0390 AC: 136 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	8.9
DANN	Benign	0.55
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2395357; hg19: chr6-33101006;