dbSNP rs3924519: TNFRSF10D:c.371-44A>G (chr8-23147116-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003840.5(TNFRSF10D):c.371-44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,539,050 control chromosomes in the GnomAD database, including 89,699 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 0.36 ( 11006 hom., cov: 31)

Exomes 𝑓: 0.32 ( 78693 hom. )

Consequence

TNFRSF10D
NM_003840.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.37

Publications

19 publications found

Variant links:

Genes affected

TNFRSF10D (HGNC:11907): (TNF receptor superfamily member 10d) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains an extracellular TRAIL-binding domain, a transmembrane domain, and a truncated cytoplamic death domain. This receptor does not induce apoptosis, and has been shown to play an inhibitory role in TRAIL-induced cell apoptosis. [provided by RefSeq, Jul 2008]

TNFRSF10D links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_003840.5, 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003840.5. 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
	TNFRSF10D	NM_003840.5	MANE Select	c.371-44A>G		intron	N/A	NP_003831.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10D	ENST00000312584.4	TSL:1 MANE Select	c.371-44A>G		intron	N/A	ENSP00000310263.3	Q9UBN6
	TNFRSF10D	ENST00000870290.1		c.371-44A>G		intron	N/A	ENSP00000540349.1

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54426

AN:

151822

Hom.:

10988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.836

Gnomad SAS

AF:

0.404

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.376

GnomAD2 exomes

AF:

0.382

AC:

95255

AN:

249314

AF XY:

0.370

show subpopulations

Gnomad AFR exome

AF:

0.421

Gnomad AMR exome

AF:

0.584

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.827

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.330

GnomAD4 exome

AF:

0.316

AC:

438197

AN:

1387110

Hom.:

78693

Cov.:

AF XY:

0.315

AC XY:

219013

AN XY:

694298

show subpopulations

African (AFR)

AF:

0.415

AC:

13207

AN:

31822

American (AMR)

AF:

0.570

AC:

25324

AN:

44464

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

5002

AN:

25590

East Asian (EAS)

AF:

0.835

AC:

32753

AN:

39202

South Asian (SAS)

AF:

0.371

AC:

31356

AN:

84562

European-Finnish (FIN)

AF:

0.267

AC:

14006

AN:

52402

Middle Eastern (MID)

AF:

0.230

AC:

1244

AN:

5404

European-Non Finnish (NFE)

AF:

0.283

AC:

296018

AN:

1045842

Other (OTH)

AF:

0.334

AC:

19287

AN:

57822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

13883

27767

41650

55534

69417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9940

19880

29820

39760

49700

<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:

0.359

AC:

54502

AN:

151940

Hom.:

11006

Cov.:

AF XY:

0.365

AC XY:

27083

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.416

AC:

17217

AN:

41384

American (AMR)

AF:

0.482

AC:

7370

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

711

AN:

3466

East Asian (EAS)

AF:

0.836

AC:

4322

AN:

5170

South Asian (SAS)

AF:

0.404

AC:

1947

AN:

4814

European-Finnish (FIN)

AF:

0.256

AC:

2705

AN:

10574

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.281

AC:

19070

AN:

67942

Other (OTH)

AF:

0.378

AC:

796

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1643

3287

4930

6574

8217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

516

1032

1548

2064

2580

<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:

0.312

Hom.:

28180

Bravo

AF:

0.382

Asia WGS

AF:

0.574

AC:

1993

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.14

(source)

DANN

Benign

0.46

PhyloP100

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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