2-161176151-T-C

Variant names:

• chr2-161176151-T-C
• rs889916
• NM_001199135.3:c.-49-3463T>C

Variant summary

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

The NM_001199135.3(TANK):​c.-49-3463T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 152,102 control chromosomes in the GnomAD database, including 49,468 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 0.80 (49468 hom., cov: 31)
• Consequence: TANK NM_001199135.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199135.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANK	NM_001199135.3	MANE Select	c.-49-3463T>C		intron	N/A	NP_001186064.1	Q92844-1
	TANK	NM_004180.3		c.-49-3463T>C		intron	N/A	NP_004171.2
	TANK	NM_133484.2		c.-49-3463T>C		intron	N/A	NP_597841.1	Q92844-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANK	ENST00000392749.7	TSL:1 MANE Select	c.-49-3463T>C		intron	N/A	ENSP00000376505.2	Q92844-1
	TANK	ENST00000259075.6	TSL:1	c.-49-3463T>C		intron	N/A	ENSP00000259075.2	Q92844-1
	TANK	ENST00000882703.1		c.-49-3463T>C		intron	N/A	ENSP00000552762.1

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122262 AN: 151984 Hom.: 49422 Cov.: 31

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.804 AC: 122366 AN: 152102 Hom.: 49468 Cov.: 31 AF XY: 0.808 AC XY: 60046 AN XY: 74350

African (AFR) AF: 0.727 AC: 30168 AN: 41470

American (AMR) AF: 0.861 AC: 13142 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2643 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5155 AN: 5176

South Asian (SAS) AF: 0.818 AC: 3948 AN: 4826

European-Finnish (FIN) AF: 0.800 AC: 8474 AN: 10588

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.827 AC: 56234 AN: 67992

Other (OTH) AF: 0.802 AC: 1696 AN: 2114

Alfa AF: 0.817 Hom.: 9948

Bravo AF: 0.809

Asia WGS AF: 0.906 AC: 3146 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.8
DANN	Benign	0.65
PhyloP100		-0.10
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: rs889916; hg19: chr2-162032662;