chr3-49828959-C-T

Variant names:

• chr3-49828959-C-T
• rs1128535
• NM_005879.3:c.*144G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005879.3(TRAIP):​c.*144G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,148,112 control chromosomes in the GnomAD database, including 126,967 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18255 hom., cov: 32)
  • Exomes 𝑓: 0.46 (108712 hom.)
• Consequence: TRAIP NM_005879.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.280
• Publications: 38 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 3-49828959-C-T is Benign according to our data. Variant chr3-49828959-C-T is described in ClinVar as Benign. ClinVar VariationId is 1271112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAIP	NM_005879.3	c.*144G>A		3_prime_UTR_variant	Exon 15 of 15	ENST00000331456.7	NP_005870.2
TRAIP	XM_017005526.2	c.*144G>A		3_prime_UTR_variant	Exon 12 of 12		XP_016861015.1
TRAIP	XM_047447240.1	c.*144G>A		3_prime_UTR_variant	Exon 10 of 10		XP_047303196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAIP	ENST00000331456.7	c.*144G>A		3_prime_UTR_variant	Exon 15 of 15	1	NM_005879.3	ENSP00000328203.2
TRAIP	ENST00000491060.1	n.708G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3
TRAIP	ENST00000473195.5	n.*727G>A		downstream_gene_variant		3		ENSP00000419556.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72565 AN: 151996 Hom.: 18231 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.479

GnomAD4 exome AF: 0.460 AC: 458080 AN: 995998 Hom.: 108712 Cov.: 13 AF XY: 0.458 AC XY: 231433 AN XY: 505202

African (AFR) AF: 0.588 AC: 14368 AN: 24416

American (AMR) AF: 0.283 AC: 11017 AN: 38936

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 7497 AN: 19256

East Asian (EAS) AF: 0.205 AC: 7549 AN: 36810

South Asian (SAS) AF: 0.372 AC: 25370 AN: 68264

European-Finnish (FIN) AF: 0.346 AC: 14127 AN: 40870

Middle Eastern (MID) AF: 0.425 AC: 1324 AN: 3116

European-Non Finnish (NFE) AF: 0.495 AC: 356708 AN: 720108

Other (OTH) AF: 0.455 AC: 20120 AN: 44222

GnomAD4 genome AF: 0.477 AC: 72630 AN: 152114 Hom.: 18255 Cov.: 32 AF XY: 0.466 AC XY: 34677 AN XY: 74384

African (AFR) AF: 0.588 AC: 24380 AN: 41486

American (AMR) AF: 0.372 AC: 5679 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1338 AN: 3468

East Asian (EAS) AF: 0.172 AC: 891 AN: 5176

South Asian (SAS) AF: 0.380 AC: 1834 AN: 4826

European-Finnish (FIN) AF: 0.333 AC: 3519 AN: 10582

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

European-Non Finnish (NFE) AF: 0.490 AC: 33273 AN: 67972

Other (OTH) AF: 0.483 AC: 1022 AN: 2116

Alfa AF: 0.499 Hom.: 2385

Bravo AF: 0.486

Asia WGS AF: 0.379 AC: 1318 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.82
DANN	Benign	0.37
PhyloP100		-0.28
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: rs1128535; hg19: chr3-49866392; COSMIC: COSV58914026; COSMIC: COSV58914026;