rs13312727

Positions:

• chr16-67154540-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000345057.9(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 ENST00000345057.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.839

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TRADD	NM_003789.4	c.*109A>C		3_prime_UTR_variant	5/5	ENST00000345057.9	NP_003780.1
TRADD	NM_001323552.2	c.*109A>C		3_prime_UTR_variant	5/5		NP_001310481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRADD	ENST00000345057.9	c.*109A>C		3_prime_UTR_variant	5/5	1	NM_003789.4	ENSP00000341268	P1
TRADD	ENST00000486556.1	c.*109A>C		3_prime_UTR_variant	3/3	2		ENSP00000462591

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 5546 AN: 152180 Hom.: 150 Cov.: 32

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.: 18 AF XY: 0.0345 AC XY: 21005 AN XY: 608406

Gnomad4 AFR exome AF: 0.0357

Gnomad4 AMR exome AF: 0.0126

Gnomad4 ASJ exome AF: 0.0123

Gnomad4 EAS exome AF: 0.00112

Gnomad4 SAS exome AF: 0.0677

Gnomad4 FIN exome AF: 0.0955

Gnomad4 NFE exome AF: 0.0316

Gnomad4 OTH exome AF: 0.0292

GnomAD4 genome AF: 0.0365 AC: 5554 AN: 152298 Hom.: 151 Cov.: 32 AF XY: 0.0404 AC XY: 3008 AN XY: 74466

Gnomad4 AFR AF: 0.0373

Gnomad4 AMR AF: 0.0163

Gnomad4 ASJ AF: 0.0109

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0667

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0318

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0288 Hom.: 73

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
DANN	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs13312727; hg19: chr16-67188443;