rs2294478

Positions:

• chr6-33131189-C-A
• chr6-33131189-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_926703.3(LOC105375021):​n.565-90G>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,098 control chromosomes in the GnomAD database, including 17,024 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 0.46 (17009 hom., cov: 32)
  • Exomes 𝑓: 0.42 (15 hom.)
• Consequence: LOC105375021 XR_926703.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430

Genes affected

LOC105375021 (HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105375021	XR_926703.3	n.565-90G>T		intron_variant, non_coding_transcript_variant
LOC105375021	XR_001744086.2	n.710+8G>T		splice_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DPA3	ENST00000454398.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69359 AN: 151836 Hom.: 16996 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.493

GnomAD4 exome AF: 0.424 AC: 61 AN: 144 Hom.: 15 Cov.: 0 AF XY: 0.429 AC XY: 42 AN XY: 98

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.625

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.440

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.457 AC: 69403 AN: 151954 Hom.: 17009 Cov.: 32 AF XY: 0.463 AC XY: 34407 AN XY: 74280

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.772

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.497

Alfa AF: 0.492 Hom.: 31241

Bravo AF: 0.459

Asia WGS AF: 0.616 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2294478; hg19: chr6-33098966;