1-211375045-T-G

Variant names:

• chr1-211375045-T-G
• rs3738200
• NM_001033910.3:c.*2343T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033910.3(TRAF5):​c.*2343T>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,222 control chromosomes in the GnomAD database, including 1,414 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 0.13 (1414 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TRAF5 NM_001033910.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF5	NM_001033910.3	c.*2343T>G		downstream_gene_variant		ENST00000261464.10	NP_001029082.1
TRAF5	NM_001319207.2	c.*2343T>G		downstream_gene_variant			NP_001306136.1
TRAF5	NM_004619.4	c.*2343T>G		downstream_gene_variant			NP_004610.1
TRAF5	NM_145759.3	c.*2343T>G		downstream_gene_variant			NP_665702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF5	ENST00000261464.10	c.*2343T>G		downstream_gene_variant		1	NM_001033910.3	ENSP00000261464.5
TRAF5	ENST00000336184.6	c.*2343T>G		downstream_gene_variant		5		ENSP00000336825.2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19755 AN: 152104 Hom.: 1410 Cov.: 32

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0513

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.130 AC: 19772 AN: 152222 Hom.: 1414 Cov.: 32 AF XY: 0.128 AC XY: 9534 AN XY: 74426

African (AFR) AF: 0.0895 AC: 3717 AN: 41544

American (AMR) AF: 0.100 AC: 1532 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 567 AN: 3464

East Asian (EAS) AF: 0.0510 AC: 265 AN: 5192

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4820

European-Finnish (FIN) AF: 0.116 AC: 1226 AN: 10590

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10942 AN: 67992

Other (OTH) AF: 0.148 AC: 312 AN: 2114

Alfa AF: 0.155 Hom.: 2857

Bravo AF: 0.126

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		3.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3738200; hg19: chr1-211548387;