3-49828959-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005879.3(TRAIP):c.*144G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,148,112 control chromosomes in the GnomAD database, including 126,967 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (18255 hom., cov: 32)
  • Exomes 𝑓: 0.46 (108712 hom.)
• Consequence: TRAIP NM_005879.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.280

Genes affected

TRAIP (HGNC:30764): (TRAF interacting protein) This gene encodes a protein that contains an N-terminal RING finger motif and a putative coiled-coil domain. A similar murine protein interacts with TNFR-associated factor 1 (TRAF1), TNFR-associated factor 2 (TRAF2), and cylindromatosis. The interaction with TRAF2 inhibits TRAF2-mediated nuclear factor kappa-B, subunit 1 activation that is required for cell activation and protection against apoptosis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 3-49828959-C-T is Benign according to our data. Variant chr3-49828959-C-T is described in ClinVar as [Benign]. Clinvar id is 1271112.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAIP	NM_005879.3	c.*144G>A		3_prime_UTR_variant	15/15	ENST00000331456.7
TRAIP	XM_017005526.2	c.*144G>A		3_prime_UTR_variant	12/12
TRAIP	XM_047447240.1	c.*144G>A		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAIP	ENST00000331456.7	c.*144G>A		3_prime_UTR_variant	15/15	1	NM_005879.3	P1
TRAIP	ENST00000491060.1	n.708G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72565 AN: 151996 Hom.: 18231 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.479

GnomAD4 exome AF: 0.460 AC: 458080 AN: 995998 Hom.: 108712 Cov.: 13 AF XY: 0.458 AC XY: 231433 AN XY: 505202

Gnomad4 AFR exome AF: 0.588

Gnomad4 AMR exome AF: 0.283

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.372

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.455

GnomAD4 genome AF: 0.477 AC: 72630 AN: 152114 Hom.: 18255 Cov.: 32 AF XY: 0.466 AC XY: 34677 AN XY: 74384

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.483

Alfa AF: 0.499 Hom.: 2385

Bravo AF: 0.486

Asia WGS AF: 0.379 AC: 1318 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.82
Dann	Benign	0.37

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: rs1128535; hg19: chr3-49866392; COSMIC: COSV58914026; COSMIC: COSV58914026;