6-32553130-T-C

Variant names:

• chr6-32553130-T-C
• rs3828840
• ENST00000411500.5:n.876-58A>G

Variant summary

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

The ENST00000411500.5(HLA-DRB6):​n.876-58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 147,840 control chromosomes in the GnomAD database, including 39,141 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 0.71 (39141 hom., cov: 27)
  • Exomes 𝑓: 0.74 (89967 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DRB6 ENST00000411500.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• Publications: 28 publications found

Genes affected

HLA-DRB6 (HGNC:):

HLA-DRB6 (HGNC:4954): (major histocompatibility complex, class II, DR beta 6 (pseudogene))

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DRB6	NR_001298.1	n.876-58A>G		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DRB6	ENST00000411500.5	n.876-58A>G		intron_variant	Intron 5 of 5	6
HLA-DRB6	ENST00000437183.5	n.967-58A>G		intron_variant	Intron 5 of 5	6
HLA-DRB6	ENST00000437650.2	n.689-58A>G		intron_variant	Intron 4 of 4	6
HLA-DRB6	ENST00000804227.1	n.949-58A>G		intron_variant	Intron 5 of 5

Frequencies

GnomAD3 genomes AF: 0.715 AC: 105623 AN: 147724 Hom.: 39106 Cov.: 27

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.824

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.740

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.743 AC: 233993 AN: 314770 Hom.: 89967 AF XY: 0.749 AC XY: 131805 AN XY: 176052

African (AFR) AF: 0.751 AC: 5120 AN: 6818

American (AMR) AF: 0.832 AC: 17522 AN: 21056

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 7385 AN: 9032

East Asian (EAS) AF: 0.775 AC: 11472 AN: 14810

South Asian (SAS) AF: 0.761 AC: 33071 AN: 43440

European-Finnish (FIN) AF: 0.634 AC: 17934 AN: 28270

Middle Eastern (MID) AF: 0.792 AC: 1661 AN: 2096

European-Non Finnish (NFE) AF: 0.739 AC: 128515 AN: 173906

Other (OTH) AF: 0.737 AC: 11313 AN: 15342

GnomAD4 genome AF: 0.715 AC: 105701 AN: 147840 Hom.: 39141 Cov.: 27 AF XY: 0.710 AC XY: 51081 AN XY: 71962

African (AFR) AF: 0.728 AC: 29005 AN: 39846

American (AMR) AF: 0.752 AC: 10959 AN: 14574

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 2662 AN: 3462

East Asian (EAS) AF: 0.762 AC: 3746 AN: 4916

South Asian (SAS) AF: 0.679 AC: 3218 AN: 4736

European-Finnish (FIN) AF: 0.597 AC: 5875 AN: 9836

Middle Eastern (MID) AF: 0.817 AC: 232 AN: 284

European-Non Finnish (NFE) AF: 0.712 AC: 47865 AN: 67212

Other (OTH) AF: 0.735 AC: 1518 AN: 2066

Alfa AF: 0.707 Hom.: 19320

Asia WGS AF: 0.657 AC: 2271 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.39
DANN	Benign	0.28
PhyloP100		-2.3

Splicing

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

Other links and lift over

dbSNP: rs3828840; hg19: chr6-32520907;