rs4428528

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 28 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.343 AC: 14214 AN: 41456

American (AMR) AF: 0.273 AC: 4178 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 821 AN: 3472

East Asian (EAS) AF: 0.245 AC: 1266 AN: 5176

South Asian (SAS) AF: 0.237 AC: 1142 AN: 4818

European-Finnish (FIN) AF: 0.355 AC: 3745 AN: 10560

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17419 AN: 67972

Other (OTH) AF: 0.285 AC: 603 AN: 2114

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
PhyloP100		-0.42

Splicing

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

Other links and lift over

dbSNP: rs4428528; hg19: chr6-32430362;