8-59120246-T-G

Variant names:

• chr8-59120246-T-G
• rs2290526
• ENST00000688120.2:n.436T>G

Variant summary

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

The ENST00000688120.2(TOX-DT):​n.436T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,666 control chromosomes in the GnomAD database, including 1,309 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 0.11 (1296 hom., cov: 32)
  • Exomes 𝑓: 0.18 (13 hom.)
• Consequence: TOX-DT ENST00000688120.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 7 publications found

Genes affected

TOX-DT (HGNC:55935): (TOX divergent transcript)

ENSG00000304217 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000688120.2. 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
	TOX-DT	NR_149030.1		n.77-90T>G		intron	N/A
	TOX-DT	NR_149031.1		n.192-90T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOX-DT	ENST00000688120.2		n.436T>G		non_coding_transcript_exon	Exon 1 of 1
	TOX-DT	ENST00000800313.1		n.349T>G		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000304217	ENST00000801110.1		n.582A>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16959 AN: 152014 Hom.: 1297 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.182 AC: 97 AN: 534 Hom.: 13 Cov.: 0 AF XY: 0.172 AC XY: 58 AN XY: 338

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.193 AC: 83 AN: 430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.132 AC: 10 AN: 76

Other (OTH) AF: 0.214 AC: 3 AN: 14

GnomAD4 genome AF: 0.111 AC: 16961 AN: 152132 Hom.: 1296 Cov.: 32 AF XY: 0.117 AC XY: 8681 AN XY: 74370

African (AFR) AF: 0.0360 AC: 1497 AN: 41538

American (AMR) AF: 0.189 AC: 2887 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1569 AN: 5124

South Asian (SAS) AF: 0.117 AC: 564 AN: 4818

European-Finnish (FIN) AF: 0.190 AC: 2008 AN: 10594

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7708 AN: 67982

Other (OTH) AF: 0.126 AC: 265 AN: 2108

Alfa AF: 0.108 Hom.: 1479

Bravo AF: 0.110

Asia WGS AF: 0.194 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.1
DANN	Benign	0.66
PhyloP100		-0.27

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: rs2290526;

hg19: chr8-60032805;

COSMIC: COSV63852091;