6-32554612-T-A

Variant names:

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

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>T 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 0.000013 (0 hom., cov: 10)
  • Exomes 𝑓: 0.000010 (1 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=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DRB6	NR_001298.1	n.740+78A>T		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>T		intron_variant	Intron 3 of 5	6
HLA-DRB6	ENST00000437183.5	n.831+7A>T		splice_region_variant, intron_variant	Intron 3 of 5	6
HLA-DRB6	ENST00000437650.2	n.553+78A>T		intron_variant	Intron 2 of 4	6
HLA-DRB6	ENST00000804227.1	n.813+78A>T		intron_variant	Intron 3 of 5

Frequencies

GnomAD3 genomes AF: 0.0000128 AC: 1 AN: 78174 Hom.: 0 Cov.: 10

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000147

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000101 AC: 4 AN: 397270 Hom.: 1 Cov.: 5 AF XY: 0.00000479 AC XY: 1 AN XY: 208842

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

African (AFR) AF: 0.00 AC: 0 AN: 9170

American (AMR) AF: 0.00 AC: 0 AN: 14006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8418

East Asian (EAS) AF: 0.000207 AC: 3 AN: 14486

South Asian (SAS) AF: 0.00 AC: 0 AN: 32464

European-Finnish (FIN) AF: 0.0000368 AC: 1 AN: 27198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 271786

Other (OTH) AF: 0.00 AC: 0 AN: 18006

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000812204), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000128 AC: 1 AN: 78254 Hom.: 0 Cov.: 10 AF XY: 0.0000264 AC XY: 1 AN XY: 37856

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

African (AFR) AF: 0.00 AC: 0 AN: 20706

American (AMR) AF: 0.000147 AC: 1 AN: 6822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1798

East Asian (EAS) AF: 0.00 AC: 0 AN: 2572

South Asian (SAS) AF: 0.00 AC: 0 AN: 2376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 152

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 36270

Other (OTH) AF: 0.00 AC: 0 AN: 1074

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.1
DANN	Benign	0.62
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;