chr8-23225458-G-C

Variant names:

• chr8-23225458-G-C
• rs13278062
• ENST00000500853.2:n.250G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000840437.1(TNFRSF10A-DT):​n.256G>C variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 143,664 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000014 (0 hom., cov: 21)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNFRSF10A-DT ENST00000840437.1 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 107 publications found

Genes affected

TNFRSF10A-DT (HGNC:52647): (TNFRSF10A divergent transcript)

ENSG00000250714 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000840437.1. 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
	TNFRSF10A-DT	NR_033928.1		n.238G>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10A-DT	ENST00000500853.2	TSL:2	n.250G>C		non_coding_transcript_exon	Exon 1 of 3
	TNFRSF10A-DT	ENST00000670072.2		n.450G>C		non_coding_transcript_exon	Exon 1 of 2
	TNFRSF10A-DT	ENST00000840437.1		n.256G>C		splice_region non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0000139 AC: 2 AN: 143664 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000303

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6844 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3532

African (AFR) AF: 0.00 AC: 0 AN: 518

American (AMR) AF: 0.00 AC: 0 AN: 162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 180

East Asian (EAS) AF: 0.00 AC: 0 AN: 624

South Asian (SAS) AF: 0.00 AC: 0 AN: 134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 30

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4450

Other (OTH) AF: 0.00 AC: 0 AN: 448

GnomAD4 genome AF: 0.0000139 AC: 2 AN: 143664 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 68970

African (AFR) AF: 0.00 AC: 0 AN: 39848

American (AMR) AF: 0.00 AC: 0 AN: 13702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.00 AC: 0 AN: 4882

South Asian (SAS) AF: 0.00 AC: 0 AN: 4304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.0000303 AC: 2 AN: 65992

Other (OTH) AF: 0.00 AC: 0 AN: 1904

Alfa AF: 0.00 Hom.: 37861

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.58
PhyloP100		-1.7
PromoterAI		-0.14	Neutral

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: rs13278062;

hg19: chr8-23082971;