2-161182061-C-G

Variant names:

• chr2-161182061-C-G
• rs1267080
• NM_001199135.3:c.99+2300C>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.99+2300C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 151,988 control chromosomes in the GnomAD database, including 51,656 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 0.82 (51656 hom., cov: 31)
• Consequence: TANK NM_001199135.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 4 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=-0.92).
• 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.99+2300C>G		intron	N/A	NP_001186064.1	Q92844-1
	TANK	NM_004180.3		c.99+2300C>G		intron	N/A	NP_004171.2
	TANK	NM_133484.2		c.99+2300C>G		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.99+2300C>G		intron	N/A	ENSP00000376505.2	Q92844-1
	TANK	ENST00000259075.6	TSL:1	c.99+2300C>G		intron	N/A	ENSP00000259075.2	Q92844-1
	TANK	ENST00000403609.1	TSL:1	c.99+2300C>G		intron	N/A	ENSP00000385983.1	Q92844-3

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125044 AN: 151870 Hom.: 51599 Cov.: 31

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.823 AC: 125158 AN: 151988 Hom.: 51656 Cov.: 31 AF XY: 0.827 AC XY: 61403 AN XY: 74270

African (AFR) AF: 0.776 AC: 32124 AN: 41396

American (AMR) AF: 0.869 AC: 13274 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2785 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5165 AN: 5186

South Asian (SAS) AF: 0.856 AC: 4121 AN: 4816

European-Finnish (FIN) AF: 0.803 AC: 8457 AN: 10538

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.833 AC: 56598 AN: 67984

Other (OTH) AF: 0.816 AC: 1724 AN: 2114

Alfa AF: 0.828 Hom.: 6088

Bravo AF: 0.828

Asia WGS AF: 0.920 AC: 3196 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.64
DANN	Benign	0.50
PhyloP100		-0.078
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: rs1267080; hg19: chr2-162038572;