3-49834208-C-T

Position:

• chr3-49834208-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
TRAIP	NM_005879.3	c.885-2140G>A		intron_variant		ENST00000331456.7
TRAIP	XM_017005526.2	c.588-2140G>A		intron_variant
TRAIP	XM_047447240.1	c.357-2140G>A		intron_variant
TRAIP	XR_007094382.1	n.996-1168G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAIP	ENST00000331456.7	c.885-2140G>A		intron_variant		1	NM_005879.3	P1
TRAIP	ENST00000469027.5	c.420-2140G>A		intron_variant		5
TRAIP	ENST00000473195.5	c.*211-4140G>A		intron_variant, NMD_transcript_variant		3
TRAIP	ENST00000475495.1	n.359-2140G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.279

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

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: rs2352967; hg19: chr3-49871641;