rs695238

Variant names:

• chr3-49831725-A-C
• rs695238
• NM_005879.3:c.1037+191T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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]

TRAIP Gene-Disease associations (from GenCC):

• Seckel syndrome 9

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Seckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005879.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAIP	NM_005879.3	MANE Select	c.1037+191T>G		intron	N/A	NP_005870.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAIP	ENST00000331456.7	TSL:1 MANE Select	c.1037+191T>G		intron	N/A	ENSP00000328203.2
	TRAIP	ENST00000469027.5	TSL:5	c.572+191T>G		intron	N/A	ENSP00000420085.1
	TRAIP	ENST00000473195.5	TSL:3	n.*211-1657T>G		intron	N/A	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

African (AFR) AF: 0.588 AC: 24377 AN: 41476

American (AMR) AF: 0.371 AC: 5664 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1339 AN: 3470

East Asian (EAS) AF: 0.174 AC: 899 AN: 5180

South Asian (SAS) AF: 0.380 AC: 1832 AN: 4824

European-Finnish (FIN) AF: 0.332 AC: 3506 AN: 10572

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33261 AN: 67956

Other (OTH) AF: 0.484 AC: 1022 AN: 2110

Alfa AF: 0.477 Hom.: 6843

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

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.032
DANN	Benign	0.45
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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