2-161207853-G-T

Variant names:

• chr2-161207853-G-T
• rs10186736
• NM_001199135.3:c.327+3060G>T

Variant summary

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

The NM_004180.3(TANK):​c.327+3060G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 985,160 control chromosomes in the GnomAD database, including 1,657 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 0.068 (1158 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (499 hom.)
• Consequence: TANK NM_004180.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004180.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANK	NM_001199135.3	MANE Select	c.327+3060G>T		intron	N/A	NP_001186064.1
	TANK	NM_004180.3		c.327+3060G>T		intron	N/A	NP_004171.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANK	ENST00000392749.7	TSL:1 MANE Select	c.327+3060G>T		intron	N/A	ENSP00000376505.2
	TANK	ENST00000259075.6	TSL:1	c.327+3060G>T		intron	N/A	ENSP00000259075.2
	TANK	ENST00000468831.5	TSL:1	n.507+3060G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0676 AC: 10277 AN: 152080 Hom.: 1145 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0295

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.0493

GnomAD4 exome AF: 0.00599 AC: 4988 AN: 832962 Hom.: 499 Cov.: 30 AF XY: 0.00571 AC XY: 2195 AN XY: 384674

African (AFR) AF: 0.246 AC: 3885 AN: 15764

American (AMR) AF: 0.0203 AC: 20 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0505 AC: 260 AN: 5148

East Asian (EAS) AF: 0.00 AC: 0 AN: 3626

South Asian (SAS) AF: 0.000182 AC: 3 AN: 16460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 276

Middle Eastern (MID) AF: 0.0124 AC: 20 AN: 1618

European-Non Finnish (NFE) AF: 0.000517 AC: 394 AN: 761790

Other (OTH) AF: 0.0149 AC: 406 AN: 27296

GnomAD4 genome AF: 0.0679 AC: 10330 AN: 152198 Hom.: 1158 Cov.: 32 AF XY: 0.0652 AC XY: 4849 AN XY: 74402

African (AFR) AF: 0.230 AC: 9546 AN: 41476

American (AMR) AF: 0.0294 AC: 450 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00113 AC: 77 AN: 68018

Other (OTH) AF: 0.0488 AC: 103 AN: 2110

Alfa AF: 0.0315 Hom.: 1032

Bravo AF: 0.0783

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.62
PhyloP100		-0.46
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: rs10186736; hg19: chr2-162064364;