2-161192690-A-G

Position:

• chr2-161192690-A-G

Variant summary

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

The NM_001199135.3(TANK):​c.100-10797A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,206 control chromosomes in the GnomAD database, including 2,247 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 0.15 (2247 hom., cov: 32)
• Consequence: TANK NM_001199135.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464

Genes affected

TANK (HGNC:11562): (TRAF family member associated NFKB activator) The TRAF (tumor necrosis factor receptor-associated factor) family of proteins associate with and transduce signals from members of the tumor necrosis factor receptor superfamily. The protein encoded by this gene is found in the cytoplasm and can bind to TRAF1, TRAF2, or TRAF3, thereby inhibiting TRAF function by sequestering the TRAFs in a latent state in the cytoplasm. For example, the protein encoded by this gene can block TRAF2 binding to LMP1, the Epstein-Barr virus transforming protein, and inhibit LMP1-mediated NF-kappa-B activation. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TANK	NM_001199135.3	c.100-10797A>G		intron_variant		ENST00000392749.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TANK	ENST00000392749.7	c.100-10797A>G		intron_variant		1	NM_001199135.3	P1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22223 AN: 152088 Hom.: 2249 Cov.: 32

Gnomad AFR AF: 0.0404

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0340

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.146 AC: 22219 AN: 152206 Hom.: 2247 Cov.: 32 AF XY: 0.142 AC XY: 10601 AN XY: 74410

Gnomad4 AFR AF: 0.0403

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.124

Alfa AF: 0.199 Hom.: 3343

Bravo AF: 0.132

Asia WGS AF: 0.0250 AC: 87 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.87
DANN	Benign	0.68

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: rs1921310; hg19: chr2-162049201; COSMIC: COSV52043677;