Genetic Variant TNFRSF10A-DT:n.250G>T (chr8-23225458-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000840437.1(TNFRSF10A-DT):n.256G>T 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 0.416 in 142,172 control chromosomes in the GnomAD database, including 14,422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.42 ( 14422 hom., cov: 21)

Exomes 𝑓: 0.20 ( 339 hom. )

Failed GnomAD Quality Control

Consequence

TNFRSF10A-DT
ENST00000840437.1 splice_region, non_coding_transcript_exon

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -1.75

Publications

107 publications found

Variant links:

Genes affected

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

TNFRSF10A-DT links:

ENSG00000250714 (HGNC:):

ENSG00000250714 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000840437.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

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>T		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

59193

AN:

142070

Hom.:

14419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.579

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.658

Gnomad EAS

AF:

0.301

Gnomad SAS

AF:

0.591

Gnomad FIN

AF:

0.533

Gnomad MID

AF:

0.507

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.437

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.199

AC:

1359

AN:

6814

Hom.:

339

Cov.:

AF XY:

0.206

AC XY:

725

AN XY:

3524

show subpopulations

African (AFR)

AF:

0.0620

AC:

AN:

516

American (AMR)

AF:

0.278

AC:

AN:

162

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

AN:

180

East Asian (EAS)

AF:

0.0801

AC:

AN:

624

South Asian (SAS)

AF:

0.523

AC:

AN:

132

European-Finnish (FIN)

AF:

0.220

AC:

AN:

296

Middle Eastern (MID)

AF:

0.200

AC:

AN:

European-Non Finnish (NFE)

AF:

0.212

AC:

938

AN:

4428

Other (OTH)

AF:

0.188

AC:

AN:

446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

127

159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.416

AC:

59205

AN:

142172

Hom.:

14422

Cov.:

AF XY:

0.419

AC XY:

28595

AN XY:

68316

show subpopulations

African (AFR)

AF:

0.175

AC:

6965

AN:

39700

American (AMR)

AF:

0.505

AC:

6843

AN:

13558

Ashkenazi Jewish (ASJ)

AF:

0.658

AC:

2211

AN:

3360

East Asian (EAS)

AF:

0.301

AC:

1451

AN:

4822

South Asian (SAS)

AF:

0.590

AC:

2497

AN:

4232

European-Finnish (FIN)

AF:

0.533

AC:

4467

AN:

8388

Middle Eastern (MID)

AF:

0.514

AC:

145

AN:

282

European-Non Finnish (NFE)

AF:

0.512

AC:

33304

AN:

65068

Other (OTH)

AF:

0.433

AC:

825

AN:

1904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

1200

2400

3600

4800

6000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

550

1100

1650

2200

2750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.479

Hom.:

37861

Bravo

AF:

0.415

Asia WGS

AF:

0.465

AC:

1620

AN:

3478

ClinVar

ClinVar submissions

Significance:not provided

Revision:no classification provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.9

(source)

DANN

Benign

0.67

PhyloP100

-1.7

PromoterAI

-0.53

Under-expression

(source)

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over