rs3769980

Variant names:

• chr2-161166332-A-G
• rs3769980
• NM_001199135.3:c.-50+5846A>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.-50+5846A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,256 control chromosomes in the GnomAD database, including 1,731 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 (1731 hom., cov: 32)
• Consequence: TANK NM_001199135.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255
• Publications: 1 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 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.-50+5846A>G		intron	N/A	NP_001186064.1	Q92844-1
	TANK	NM_004180.3		c.-49-13282A>G		intron	N/A	NP_004171.2
	TANK	NM_133484.2		c.-49-13282A>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.-50+5846A>G		intron	N/A	ENSP00000376505.2	Q92844-1
	TANK	ENST00000259075.6	TSL:1	c.-49-13282A>G		intron	N/A	ENSP00000259075.2	Q92844-1
	TANK	ENST00000882703.1		c.-50+5848A>G		intron	N/A	ENSP00000552762.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17362 AN: 152136 Hom.: 1713 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.0625

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0834

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0385

Gnomad OTH AF: 0.0908

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

GnomAD4 genome AF: 0.115 AC: 17434 AN: 152256 Hom.: 1731 Cov.: 32 AF XY: 0.116 AC XY: 8650 AN XY: 74462

African (AFR) AF: 0.259 AC: 10763 AN: 41518

American (AMR) AF: 0.0780 AC: 1193 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 217 AN: 3470

East Asian (EAS) AF: 0.176 AC: 912 AN: 5182

South Asian (SAS) AF: 0.0839 AC: 405 AN: 4828

European-Finnish (FIN) AF: 0.104 AC: 1108 AN: 10616

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0385 AC: 2620 AN: 68022

Other (OTH) AF: 0.0960 AC: 203 AN: 2114

Alfa AF: 0.0848 Hom.: 185

Bravo AF: 0.119

Asia WGS AF: 0.188 AC: 651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.65
PhyloP100		0.26
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3769980;

hg19: chr2-162022843;