chr9-120903623-T-A

Position:

• chr9-120903623-T-A

Variant summary

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

The NM_005658.5(TRAF1):​c.*1397A>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 0.447 in 152,284 control chromosomes in the GnomAD database, including 18,024 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 0.45 (17988 hom., cov: 32)
  • Exomes 𝑓: 0.52 (36 hom.)
• Consequence: TRAF1 NM_005658.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

Genes affected

TRAF1 (HGNC:12031): (TNF receptor associated factor 1) The protein encoded by this gene is a member of the TNF receptor (TNFR) associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from various receptors of the TNFR superfamily. This protein and TRAF2 form a heterodimeric complex, which is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF2 also interacts with inhibitor-of-apoptosis proteins (IAPs), and thus mediates the anti-apoptotic signals from TNF receptors. The expression of this protein can be induced by Epstein-Barr virus (EBV). EBV infection membrane protein 1 (LMP1) is found to interact with this and other TRAF proteins; this interaction is thought to link LMP1-mediated B lymphocyte transformation to the signal transduction from TNFR family receptors. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

PHF19 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF1	NM_005658.5	c.*1397A>T		3_prime_UTR_variant	8/8	ENST00000373887.8	NP_005649.1
PHF19	XM_017014612.3	c.-1749A>T		5_prime_UTR_variant	1/15		XP_016870101.1
TRAF1	NM_001190945.2	c.*1397A>T		3_prime_UTR_variant	9/9		NP_001177874.1
TRAF1	NM_001190947.2	c.*1397A>T		3_prime_UTR_variant	6/6		NP_001177876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF1	ENST00000373887.8	c.*1397A>T		3_prime_UTR_variant	8/8	1	NM_005658.5	ENSP00000362994	P1
TRAF1	ENST00000540010.1	c.*1397A>T		3_prime_UTR_variant	9/9	1		ENSP00000443183	P1
TRAF1	ENST00000546084.5	c.*1397A>T		3_prime_UTR_variant	6/6	2		ENSP00000438583

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67932 AN: 151920 Hom.: 17976 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.517

GnomAD4 exome AF: 0.525 AC: 128 AN: 244 Hom.: 36 Cov.: 0 AF XY: 0.543 AC XY: 101 AN XY: 186

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.833

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.447 AC: 67952 AN: 152040 Hom.: 17988 Cov.: 32 AF XY: 0.454 AC XY: 33706 AN XY: 74320

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.517

Alfa AF: 0.491 Hom.: 2517

Bravo AF: 0.434

Asia WGS AF: 0.559 AC: 1941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.34
DANN	Benign	0.67

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: rs4836834; hg19: chr9-123665901;