3-49834208-C-T

Variant names:

• chr3-49834208-C-T
• rs2352967
• NM_005879.3:c.885-2140G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005879.3(TRAIP):​c.885-2140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,018 control chromosomes in the GnomAD database, including 6,023 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 0.28 (6023 hom., cov: 31)
• Consequence: TRAIP NM_005879.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAIP	NM_005879.3	c.885-2140G>A		intron_variant	Intron 10 of 14	ENST00000331456.7	NP_005870.2
TRAIP	XM_017005526.2	c.588-2140G>A		intron_variant	Intron 7 of 11		XP_016861015.1
TRAIP	XM_047447240.1	c.357-2140G>A		intron_variant	Intron 5 of 9		XP_047303196.1
TRAIP	XR_007094382.1	n.996-1168G>A		intron_variant	Intron 10 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAIP	ENST00000331456.7	c.885-2140G>A		intron_variant	Intron 10 of 14	1	NM_005879.3	ENSP00000328203.2
TRAIP	ENST00000469027.5	c.420-2140G>A		intron_variant	Intron 5 of 8	5		ENSP00000420085.1
TRAIP	ENST00000473195.5	n.*211-4140G>A		intron_variant	Intron 6 of 9	3		ENSP00000419556.1
TRAIP	ENST00000475495.1	n.359-2140G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41922 AN: 151900 Hom.: 6010 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.276 AC: 41950 AN: 152018 Hom.: 6023 Cov.: 31 AF XY: 0.272 AC XY: 20192 AN XY: 74286

African (AFR) AF: 0.257 AC: 10650 AN: 41452

American (AMR) AF: 0.224 AC: 3419 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3468

East Asian (EAS) AF: 0.164 AC: 848 AN: 5174

South Asian (SAS) AF: 0.315 AC: 1514 AN: 4806

European-Finnish (FIN) AF: 0.243 AC: 2570 AN: 10560

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21126 AN: 67966

Other (OTH) AF: 0.279 AC: 589 AN: 2114

Alfa AF: 0.137 Hom.: 264

Bravo AF: 0.273

Asia WGS AF: 0.320 AC: 1110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.57
PhyloP100		-1.2
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: rs2352967; hg19: chr3-49871641;