dbSNP rs13312727: TRADD:c.*109A>C (chr16-67154540-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003789.4(TRADD):c.*109A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0341 in 1,374,018 control chromosomes in the GnomAD database, including 1,112 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 0.036 ( 151 hom., cov: 32)

Exomes 𝑓: 0.034 ( 961 hom. )

Consequence

TRADD
NM_003789.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.839

Publications

9 publications found

Variant links:

Genes affected

TRADD (HGNC:12030): (TNFRSF1A associated via death domain) The protein encoded by this gene is a death domain containing adaptor molecule that interacts with TNFRSF1A/TNFR1 and mediates programmed cell death signaling and NF-kappaB activation. This protein binds adaptor protein TRAF2, reduces the recruitment of inhibitor-of-apoptosis proteins (IAPs) by TRAF2, and thus suppresses TRAF2 mediated apoptosis. This protein can also interact with receptor TNFRSF6/FAS and adaptor protein FADD/MORT1, and is involved in the Fas-induced cell death pathway. [provided by RefSeq, Jul 2008]

TRADD links:

Genome browser will be placed here

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=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRADD	NM_003789.4 link	c.*109A>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000345057.9	NP_003780.1
TRADD	NM_001323552.2 link	c.*109A>C		3_prime_UTR_variant	Exon 5 of 5		NP_001310481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRADD	ENST00000345057.9 link	c.*109A>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_003789.4	ENSP00000341268.4
TRADD	ENST00000486556.1 link	c.*109A>C		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000462591.1

Frequencies

GnomAD3 genomes

AF:

0.0364

AC:

5546

AN:

152180

Hom.:

150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0371

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0667

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0318

Gnomad OTH

AF:

0.0205

GnomAD4 exome

AF:

0.0338

AC:

41306

AN:

1221720

Hom.:

961

Cov.:

AF XY:

0.0345

AC XY:

21005

AN XY:

608406

show subpopulations

African (AFR)

AF:

0.0357

AC:

1009

AN:

28298

American (AMR)

AF:

0.0126

AC:

444

AN:

35222

Ashkenazi Jewish (ASJ)

AF:

0.0123

AC:

291

AN:

23712

East Asian (EAS)

AF:

0.00112

AC:

AN:

34822

South Asian (SAS)

AF:

0.0677

AC:

5050

AN:

74608

European-Finnish (FIN)

AF:

0.0955

AC:

3361

AN:

35212

Middle Eastern (MID)

AF:

0.0139

AC:

AN:

4524

European-Non Finnish (NFE)

AF:

0.0316

AC:

29522

AN:

933078

Other (OTH)

AF:

0.0292

AC:

1527

AN:

52244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2094

4187

6281

8374

10468

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1076

2152

3228

4304

5380

<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:

0.0365

AC:

5554

AN:

152298

Hom.:

151

Cov.:

AF XY:

0.0404

AC XY:

3008

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0373

AC:

1549

AN:

41570

American (AMR)

AF:

0.0163

AC:

250

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0109

AC:

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5184

South Asian (SAS)

AF:

0.0667

AC:

322

AN:

4824

European-Finnish (FIN)

AF:

0.110

AC:

1160

AN:

10592

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0318

AC:

2165

AN:

68026

Other (OTH)

AF:

0.0203

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

269

538

806

1075

1344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0284

Hom.:

Bravo

AF:

0.0283

Asia WGS

AF:

0.0540

AC:

187

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.3

(source)

DANN

Benign

0.72

PhyloP100

-0.84

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over