3-49853180-C-T

Variant names:

• chr3-49853180-C-T
• rs2352974
• NM_005879.3:c.98+3176G>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.98+3176G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,424 control chromosomes in the GnomAD database, including 16,647 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 0.46 (16647 hom., cov: 32)
• Consequence: TRAIP NM_005879.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 36 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAIP	NM_005879.3	c.98+3176G>A		intron_variant	Intron 1 of 14	ENST00000331456.7	NP_005870.2
TRAIP	XM_017005526.2	c.98+3176G>A		intron_variant	Intron 1 of 11		XP_016861015.1
TRAIP	XR_007094382.1	n.209+3176G>A		intron_variant	Intron 1 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAIP	ENST00000331456.7	c.98+3176G>A		intron_variant	Intron 1 of 14	1	NM_005879.3	ENSP00000328203.2

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69479 AN: 151320 Hom.: 16624 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.459 AC: 69541 AN: 151424 Hom.: 16647 Cov.: 32 AF XY: 0.449 AC XY: 33177 AN XY: 73930

African (AFR) AF: 0.547 AC: 22594 AN: 41336

American (AMR) AF: 0.363 AC: 5525 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1313 AN: 3460

East Asian (EAS) AF: 0.174 AC: 894 AN: 5152

South Asian (SAS) AF: 0.370 AC: 1769 AN: 4776

European-Finnish (FIN) AF: 0.327 AC: 3375 AN: 10322

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32413 AN: 67860

Other (OTH) AF: 0.465 AC: 981 AN: 2110

Alfa AF: 0.469 Hom.: 3589

Bravo AF: 0.466

Asia WGS AF: 0.365 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.75
DANN	Benign	0.25
PhyloP100		-1.3
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: rs2352974; hg19: chr3-49890613;