2-238399408-A-T

Position:

• chr2-238399408-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015650.4(TRAF3IP1):​c.*489A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 152,788 control chromosomes in the GnomAD database, including 413 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 0.067 (412 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1 hom.)
• Consequence: TRAF3IP1 NM_015650.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318

Genes affected

TRAF3IP1 (HGNC:17861): (TRAF3 interacting protein 1) The protein encoded by this gene interacts with TNF receptor-associated factor 3, tethering it to cytoskeletal microtubules. The encoded protein is also an inhibitor of the innate type I IFN response. Defects in this gene are a cause of Senior-Loken syndrome 9. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF3IP1	NM_015650.4	c.*489A>T		3_prime_UTR_variant	17/17	ENST00000373327.5	NP_056465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF3IP1	ENST00000373327.5	c.*489A>T		3_prime_UTR_variant	17/17	1	NM_015650.4	ENSP00000362424.4
TRAF3IP1	ENST00000391993.7	c.*489A>T		3_prime_UTR_variant	15/15	1		ENSP00000375851.3

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 10179 AN: 152160 Hom.: 412 Cov.: 32

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0428

Gnomad ASJ AF: 0.0478

Gnomad EAS AF: 0.0463

Gnomad SAS AF: 0.0454

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0813

Gnomad OTH AF: 0.0593

GnomAD4 exome AF: 0.0451 AC: 23 AN: 510 Hom.: 1 Cov.: 0 AF XY: 0.0610 AC XY: 15 AN XY: 246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0283

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0520

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0669 AC: 10182 AN: 152278 Hom.: 412 Cov.: 32 AF XY: 0.0678 AC XY: 5045 AN XY: 74448

Gnomad4 AFR AF: 0.0411

Gnomad4 AMR AF: 0.0428

Gnomad4 ASJ AF: 0.0478

Gnomad4 EAS AF: 0.0462

Gnomad4 SAS AF: 0.0456

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.0813

Gnomad4 OTH AF: 0.0601

Alfa AF: 0.0348 Hom.: 27

Bravo AF: 0.0580

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.3
DANN	Benign	0.85

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: rs11900963; hg19: chr2-239308049;