chr2-161166332-A-G

Position:

• chr2-161166332-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.-50+5846A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,256 control chromosomes in the GnomAD database, including 1,731 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 (1731 hom., cov: 32)
• Consequence: TANK NM_001199135.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TANK	NM_001199135.3	c.-50+5846A>G		intron_variant		ENST00000392749.7	NP_001186064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TANK	ENST00000392749.7	c.-50+5846A>G		intron_variant		1	NM_001199135.3	ENSP00000376505	P1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17362 AN: 152136 Hom.: 1713 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.0625

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0834

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0385

Gnomad OTH AF: 0.0908

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

GnomAD4 genome AF: 0.115 AC: 17434 AN: 152256 Hom.: 1731 Cov.: 32 AF XY: 0.116 AC XY: 8650 AN XY: 74462

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.0780

Gnomad4 ASJ AF: 0.0625

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.0839

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0385

Gnomad4 OTH AF: 0.0960

Alfa AF: 0.0798 Hom.: 165

Bravo AF: 0.119

Asia WGS AF: 0.188 AC: 651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.65

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: rs3769980; hg19: chr2-162022843;