2-161162132-A-C

Variant names:

• chr2-161162132-A-C
• rs1267059
• NM_001199135.3:c.-50+1646A>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.-50+1646A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,958 control chromosomes in the GnomAD database, including 38,382 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 0.70 (38382 hom., cov: 32)
• Consequence: TANK NM_001199135.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 6 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANK	NM_001199135.3	c.-50+1646A>C		intron_variant	Intron 1 of 7	ENST00000392749.7	NP_001186064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANK	ENST00000392749.7	c.-50+1646A>C		intron_variant	Intron 1 of 7	1	NM_001199135.3	ENSP00000376505.2

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105770 AN: 151840 Hom.: 38383 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.696 AC: 105803 AN: 151958 Hom.: 38382 Cov.: 32 AF XY: 0.699 AC XY: 51881 AN XY: 74264

African (AFR) AF: 0.472 AC: 19553 AN: 41440

American (AMR) AF: 0.794 AC: 12121 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2439 AN: 3468

East Asian (EAS) AF: 0.820 AC: 4250 AN: 5184

South Asian (SAS) AF: 0.752 AC: 3631 AN: 4830

European-Finnish (FIN) AF: 0.717 AC: 7556 AN: 10538

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53866 AN: 67918

Other (OTH) AF: 0.708 AC: 1495 AN: 2112

Alfa AF: 0.766 Hom.: 177663

Bravo AF: 0.695

Asia WGS AF: 0.726 AC: 2515 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.9
DANN	Benign	0.81
PhyloP100		0.023
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1267059; hg19: chr2-162018643;