6-32554612-T-G

Variant names:

• chr6-32554612-T-G
• rs36149991
• ENST00000411500.5:n.740+78A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000411500.5(HLA-DRB6):​n.740+78A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.76 (22872 hom., cov: 10)
  • Exomes 𝑓: 0.71 (114978 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DRB6 ENST00000411500.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459
• Publications: 5 publications found

Genes affected

HLA-DRB6 (HGNC:):

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DRB6	NR_001298.1	n.740+78A>C		intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DRB6	ENST00000411500.5	n.740+78A>C		intron_variant	Intron 3 of 5	6
HLA-DRB6	ENST00000437183.5	n.831+7A>C		splice_region_variant, intron_variant	Intron 3 of 5	6
HLA-DRB6	ENST00000437650.2	n.553+78A>C		intron_variant	Intron 2 of 4	6
HLA-DRB6	ENST00000804227.1	n.813+78A>C		intron_variant	Intron 3 of 5

Frequencies

GnomAD3 genomes AF: 0.761 AC: 53066 AN: 69770 Hom.: 22844 Cov.: 10

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.897

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.813

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.715 AC: 269778 AN: 377464 Hom.: 114978 Cov.: 5 AF XY: 0.717 AC XY: 141646 AN XY: 197442

African (AFR) AF: 0.714 AC: 6168 AN: 8634

American (AMR) AF: 0.827 AC: 10872 AN: 13146

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 7138 AN: 8134

East Asian (EAS) AF: 0.694 AC: 9415 AN: 13576

South Asian (SAS) AF: 0.680 AC: 20230 AN: 29742

European-Finnish (FIN) AF: 0.789 AC: 20302 AN: 25744

Middle Eastern (MID) AF: 0.710 AC: 1122 AN: 1580

European-Non Finnish (NFE) AF: 0.702 AC: 182474 AN: 259860

Other (OTH) AF: 0.707 AC: 12057 AN: 17048

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.761 AC: 53122 AN: 69846 Hom.: 22872 Cov.: 10 AF XY: 0.758 AC XY: 25673 AN XY: 33850

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.751 AC: 14015 AN: 18654

American (AMR) AF: 0.794 AC: 4967 AN: 6252

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 1471 AN: 1658

East Asian (EAS) AF: 0.707 AC: 1592 AN: 2252

South Asian (SAS) AF: 0.631 AC: 1328 AN: 2106

European-Finnish (FIN) AF: 0.797 AC: 4420 AN: 5544

Middle Eastern (MID) AF: 0.896 AC: 120 AN: 134

European-Non Finnish (NFE) AF: 0.755 AC: 23987 AN: 31770

Other (OTH) AF: 0.801 AC: 785 AN: 980

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.572 Hom.: 365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	8.8
DANN	Benign	0.60
PhyloP100		-0.46

Splicing

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

Other links and lift over

dbSNP: rs36149991; hg19: chr6-32522389;