rs7568498

Positions:

• chr2-161172602-T-G

Variant summary

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

The NM_001199135.3(TANK):​c.-49-7012T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,182 control chromosomes in the GnomAD database, including 1,269 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 0.11 (1269 hom., cov: 31)
• Consequence: TANK NM_001199135.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TANK	NM_001199135.3	c.-49-7012T>G		intron_variant		ENST00000392749.7	NP_001186064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TANK	ENST00000392749.7	c.-49-7012T>G		intron_variant		1	NM_001199135.3	ENSP00000376505	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16718 AN: 152064 Hom.: 1267 Cov.: 31

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.110 AC: 16722 AN: 152182 Hom.: 1269 Cov.: 31 AF XY: 0.107 AC XY: 7990 AN XY: 74420

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0398

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.133

Alfa AF: 0.150 Hom.: 1316

Bravo AF: 0.105

Asia WGS AF: 0.0240 AC: 88 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.71

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: rs7568498; hg19: chr2-162029113;