2-161200507-T-A

Position:

• chr2-161200507-T-A

Variant summary

Our verdict is Benign. Variant got -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

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]

TANK (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TANK	NM_001199135.3	c.100-2980T>A		intron_variant		ENST00000392749.7	NP_001186064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TANK	ENST00000392749.7	c.100-2980T>A		intron_variant		1	NM_001199135.3	ENSP00000376505.2

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

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.0571

Gnomad4 ASJ exome AF: 0.0698

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.0752

Gnomad4 FIN exome AF: 0.0580

Gnomad4 NFE exome AF: 0.0362

Gnomad4 OTH exome AF: 0.0619

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

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.0625

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.0842

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0386

Gnomad4 OTH AF: 0.0963

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs3754972; hg19: chr2-162057018;