6-33139974-T-G

Variant names:

• chr6-33139974-T-G
• rs6457721
• ENST00000454398.1:n.102+3250A>C

Variant summary

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

The NR_190905.1(LOC105375021):​n.212-225A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,134 control chromosomes in the GnomAD database, including 3,419 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 0.19 (3419 hom., cov: 33)
• Consequence: LOC105375021 NR_190905.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293

Genes affected

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

LOC105375021 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375021	NR_190905.1	n.212-225A>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPA3	ENST00000454398.1	n.102+3250A>C		intron_variant	Intron 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29630 AN: 152016 Hom.: 3406 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.195 AC: 29664 AN: 152134 Hom.: 3419 Cov.: 33 AF XY: 0.198 AC XY: 14747 AN XY: 74358

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.212

Alfa AF: 0.194 Hom.: 2880

Bravo AF: 0.207

Asia WGS AF: 0.253 AC: 880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6457721; hg19: chr6-33107751;