ENST00000449413.1:n.77-2498G>C

Variant names:

• chr6-32462585-C-G
• rs4428528
• ENST00000449413.1:n.77-2498G>C

Variant summary

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

The ENST00000449413.1(HLA-DRB9):​n.77-2498G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,064 control chromosomes in the GnomAD database, including 6,397 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 (6397 hom., cov: 31)
• Consequence: HLA-DRB9 ENST00000449413.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419

Genes affected

HLA-DRB9 (HGNC:4957): (major histocompatibility complex, class II, DR beta 9 (pseudogene))

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DRB9	ENST00000449413.1	n.77-2498G>C		intron_variant	Intron 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43531 AN: 151946 Hom.: 6393 Cov.: 31

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.286 AC: 43564 AN: 152064 Hom.: 6397 Cov.: 31 AF XY: 0.287 AC XY: 21334 AN XY: 74330

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.285

Alfa AF: 0.262 Hom.: 2977

Bravo AF: 0.282

Asia WGS AF: 0.278 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4428528; hg19: chr6-32430362;