rs695238

Positions:

• chr3-49831725-A-C
• chr3-49831725-A-G

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.1037+191T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,076 control chromosomes in the GnomAD database, including 18,246 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (18246 hom., cov: 32)
• Consequence: TRAIP NM_005879.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.08

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=-0.94).
• BP6: Variant 3-49831725-A-C is Benign according to our data. Variant chr3-49831725-A-C is described in ClinVar as [Benign]. Clinvar id is 1295696.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAIP	NM_005879.3	c.1037+191T>G		intron_variant		ENST00000331456.7	NP_005870.2
TRAIP	XM_017005526.2	c.740+191T>G		intron_variant			XP_016861015.1
TRAIP	XM_047447240.1	c.509+191T>G		intron_variant			XP_047303196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAIP	ENST00000331456.7	c.1037+191T>G		intron_variant		1	NM_005879.3	ENSP00000328203.2
TRAIP	ENST00000469027.5	c.572+191T>G		intron_variant		5		ENSP00000420085.1
TRAIP	ENST00000473195.5	n.*211-1657T>G		intron_variant		3		ENSP00000419556.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72529 AN: 151958 Hom.: 18222 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.481

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.477 AC: 72594 AN: 152076 Hom.: 18246 Cov.: 32 AF XY: 0.466 AC XY: 34656 AN XY: 74362

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.484

Alfa AF: 0.495 Hom.: 4197

Bravo AF: 0.486

Asia WGS AF: 0.379 AC: 1319 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	-0.94
CADD	Benign	0.032
DANN	Benign	0.45

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: rs695238; hg19: chr3-49869158; COSMIC: COSV58913315; COSMIC: COSV58913315;