chr1-211358718-A-T

Position:

• chr1-211358718-A-T

Variant summary

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

The NM_001033910.3(TRAF5):​c.379-1194A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 149,292 control chromosomes in the GnomAD database, including 31,858 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 0.63 (31858 hom., cov: 28)
  • Failed GnomAD Quality Control
• Consequence: TRAF5 NM_001033910.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

Genes affected

TRAF5 (HGNC:12035): (TNF receptor associated factor 5) The scaffold protein encoded by this gene is a member of the tumor necrosis factor receptor-associated factor (TRAF) protein family and contains a meprin and TRAF homology (MATH) domain, a RING-type zinc finger, and two TRAF-type zinc fingers. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. This protein is one of the components of a multiple protein complex which binds to tumor necrosis factor (TNF) receptor cytoplasmic domains and mediates TNF-induced activation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAF5	NM_001033910.3	c.379-1194A>T		intron_variant		ENST00000261464.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAF5	ENST00000261464.10	c.379-1194A>T		intron_variant		1	NM_001033910.3	P1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 93600 AN: 149250 Hom.: 31856 Cov.: 28

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.642

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.627 AC: 93606 AN: 149292 Hom.: 31858 Cov.: 28 AF XY: 0.631 AC XY: 45964 AN XY: 72830

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.645

Alfa AF: 0.685 Hom.: 4648

Bravo AF: 0.608

Asia WGS AF: 0.637 AC: 2215 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.17

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: rs6684874; hg19: chr1-211532060;