rs1921310

Variant names:

• chr2-161192690-A-G
• rs1921310
• NM_001199135.3:c.100-10797A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TANK	NM_001199135.3	c.100-10797A>G		intron_variant	Intron 2 of 7	ENST00000392749.7	NP_001186064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANK	ENST00000392749.7	c.100-10797A>G		intron_variant	Intron 2 of 7	1	NM_001199135.3	ENSP00000376505.2

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

African (AFR) AF: 0.0403 AC: 1674 AN: 41568

American (AMR) AF: 0.114 AC: 1741 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0836 AC: 290 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5192

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4824

European-Finnish (FIN) AF: 0.219 AC: 2315 AN: 10570

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15649 AN: 67960

Other (OTH) AF: 0.124 AC: 263 AN: 2114

Alfa AF: 0.192 Hom.: 4161

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
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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