chr1-209778257-G-A

Position:

• chr1-209778257-G-A

Variant summary

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

The NM_025228.4(TRAF3IP3):​c.1252+84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0522 in 1,128,674 control chromosomes in the GnomAD database, including 5,691 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 0.091 (1313 hom., cov: 32)
  • Exomes 𝑓: 0.046 (4378 hom.)
• Consequence: TRAF3IP3 NM_025228.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

Genes affected

TRAF3IP3 (HGNC:30766): (TRAF3 interacting protein 3) The gene encodes a protein that mediates cell growth by modulating the c-Jun N-terminal kinase signal transduction pathway. The encoded protein may also interact with a large multi-protein assembly containing the phosphatase 2A catalytic subunit. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

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 (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF3IP3	NM_025228.4	c.1252+84G>A		intron_variant		ENST00000367025.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF3IP3	ENST00000367025.8	c.1252+84G>A		intron_variant		1	NM_025228.4	P1

Frequencies

GnomAD3 genomes AF: 0.0909 AC: 13823 AN: 152060 Hom.: 1306 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.0879

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0727

GnomAD4 exome AF: 0.0461 AC: 45014 AN: 976498 Hom.: 4378 Cov.: 13 AF XY: 0.0448 AC XY: 22580 AN XY: 503882

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.0247

Gnomad4 EAS exome AF: 0.338

Gnomad4 SAS exome AF: 0.0778

Gnomad4 FIN exome AF: 0.0147

Gnomad4 NFE exome AF: 0.0140

Gnomad4 OTH exome AF: 0.0527

GnomAD4 genome AF: 0.0910 AC: 13848 AN: 152176 Hom.: 1313 Cov.: 32 AF XY: 0.0936 AC XY: 6961 AN XY: 74402

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.0871

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.0724

Alfa AF: 0.0506 Hom.: 175

Bravo AF: 0.109

Asia WGS AF: 0.164 AC: 569 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	0.29
DANN	Benign	0.60

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: rs12083685; hg19: chr1-209951602;