rs3754972

Variant names:

• chr2-161200507-T-A
• rs3754972
• NM_001199135.3:c.100-2980T>A

Variant summary

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

The NM_001199135.3(TANK):​c.100-2980T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0539 in 980,758 control chromosomes in the GnomAD database, including 2,975 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 (1687 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1288 hom.)
• Consequence: TANK NM_001199135.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANK	NM_001199135.3	MANE Select	c.100-2980T>A		intron	N/A	NP_001186064.1
	TANK	NM_004180.3		c.100-2980T>A		intron	N/A	NP_004171.2
	TANK	NM_133484.2		c.100-2980T>A		intron	N/A	NP_597841.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANK	ENST00000392749.7	TSL:1 MANE Select	c.100-2980T>A		intron	N/A	ENSP00000376505.2
	TANK	ENST00000259075.6	TSL:1	c.100-2980T>A		intron	N/A	ENSP00000259075.2
	TANK	ENST00000403609.1	TSL:1	c.100-2980T>A		intron	N/A	ENSP00000385983.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17226 AN: 152080 Hom.: 1669 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.0625

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0837

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0386

Gnomad OTH AF: 0.0911

GnomAD4 exome AF: 0.0430 AC: 35588 AN: 828560 Hom.: 1288 Cov.: 18 AF XY: 0.0424 AC XY: 16217 AN XY: 382824

African (AFR) AF: 0.261 AC: 4062 AN: 15540

American (AMR) AF: 0.0571 AC: 56 AN: 980

Ashkenazi Jewish (ASJ) AF: 0.0698 AC: 358 AN: 5132

East Asian (EAS) AF: 0.182 AC: 655 AN: 3594

South Asian (SAS) AF: 0.0752 AC: 1228 AN: 16326

European-Finnish (FIN) AF: 0.0580 AC: 16 AN: 276

Middle Eastern (MID) AF: 0.0378 AC: 61 AN: 1612

European-Non Finnish (NFE) AF: 0.0362 AC: 27472 AN: 757958

Other (OTH) AF: 0.0619 AC: 1680 AN: 27142

GnomAD4 genome AF: 0.114 AC: 17297 AN: 152198 Hom.: 1687 Cov.: 32 AF XY: 0.115 AC XY: 8576 AN XY: 74420

African (AFR) AF: 0.256 AC: 10630 AN: 41494

American (AMR) AF: 0.0777 AC: 1189 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 217 AN: 3472

East Asian (EAS) AF: 0.176 AC: 914 AN: 5190

South Asian (SAS) AF: 0.0842 AC: 406 AN: 4824

European-Finnish (FIN) AF: 0.104 AC: 1102 AN: 10586

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

European-Non Finnish (NFE) AF: 0.0386 AC: 2623 AN: 68024

Other (OTH) AF: 0.0963 AC: 203 AN: 2108

Alfa AF: 0.0794 Hom.: 128

Bravo AF: 0.118

Asia WGS AF: 0.188 AC: 648 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.38
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: rs3754972; hg19: chr2-162057018;