6-32462731-C-T

Variant names:

• chr6-32462731-C-T
• rs4434496
• ENST00000449413.1:n.77-2644G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000449413.1(HLA-DRB9):​n.77-2644G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,012 control chromosomes in the GnomAD database, including 6,402 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 (6402 hom., cov: 31)
• Consequence: HLA-DRB9 ENST00000449413.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• Publications: 18 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000449413.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRB9	ENST00000449413.1	TSL:6	n.77-2644G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43521 AN: 151894 Hom.: 6398 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: 0.238

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.287 AC: 43554 AN: 152012 Hom.: 6402 Cov.: 31 AF XY: 0.287 AC XY: 21336 AN XY: 74310

African (AFR) AF: 0.343 AC: 14212 AN: 41406

American (AMR) AF: 0.273 AC: 4181 AN: 15290

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

East Asian (EAS) AF: 0.244 AC: 1262 AN: 5162

South Asian (SAS) AF: 0.237 AC: 1145 AN: 4822

European-Finnish (FIN) AF: 0.354 AC: 3744 AN: 10568

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

European-Non Finnish (NFE) AF: 0.256 AC: 17410 AN: 67974

Other (OTH) AF: 0.286 AC: 603 AN: 2112

Alfa AF: 0.236 Hom.: 1413

Bravo AF: 0.282

Asia WGS AF: 0.278 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.4
DANN	Benign	0.73
PhyloP100		0.11

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4434496;

hg19: chr6-32430508;