rs1267034

Positions:

• chr2-161216227-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001199135.3(TANK):​c.328-7688A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,210 control chromosomes in the GnomAD database, including 890 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 0.10 (890 hom., cov: 32)
• Consequence: TANK NM_001199135.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TANK	NM_001199135.3	c.328-7688A>G		intron_variant		ENST00000392749.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TANK	ENST00000392749.7	c.328-7688A>G		intron_variant		1	NM_001199135.3	P1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15907 AN: 152092 Hom.: 892 Cov.: 32

Gnomad AFR AF: 0.0687

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.0756

Gnomad SAS AF: 0.0870

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.104 AC: 15905 AN: 152210 Hom.: 890 Cov.: 32 AF XY: 0.104 AC XY: 7760 AN XY: 74412

Gnomad4 AFR AF: 0.0686

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.0758

Gnomad4 SAS AF: 0.0866

Gnomad4 FIN AF: 0.0969

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.103

Alfa AF: 0.125 Hom.: 1559

Bravo AF: 0.102

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1267034; hg19: chr2-162072738; COSMIC: COSV52043302;