rs1267034

Variant names:

• chr2-161216227-A-G
• rs1267034
• NM_001199135.3:c.328-7688A>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.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
• Publications: 11 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=-0.89).
• 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 rank	MANE	Protein	UniProt
TANK	NM_001199135.3	c.328-7688A>G		intron_variant	Intron 4 of 7	ENST00000392749.7	NP_001186064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANK	ENST00000392749.7	c.328-7688A>G		intron_variant	Intron 4 of 7	1	NM_001199135.3	ENSP00000376505.2

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

African (AFR) AF: 0.0686 AC: 2849 AN: 41556

American (AMR) AF: 0.105 AC: 1609 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 335 AN: 3472

East Asian (EAS) AF: 0.0758 AC: 393 AN: 5184

South Asian (SAS) AF: 0.0866 AC: 418 AN: 4826

European-Finnish (FIN) AF: 0.0969 AC: 1025 AN: 10580

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.129 AC: 8753 AN: 67986

Other (OTH) AF: 0.103 AC: 217 AN: 2116

Alfa AF: 0.122 Hom.: 1909

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
PhyloP100		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1267034; hg19: chr2-162072738; COSMIC: COSV52043302;