chr2-161156444-A-G

Position:

• chr2-161156444-A-G

Variant summary

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

The NM_004180.3(TANK):​c.-50+19381A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 858,964 control chromosomes in the GnomAD database, including 891 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 0.041 (278 hom., cov: 32)
  • Exomes 𝑓: 0.037 (613 hom.)
• Consequence: TANK NM_004180.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TANK	NM_004180.3	c.-50+19381A>G		intron_variant			NP_004171.2
TANK	NM_133484.2	c.-50+19381A>G		intron_variant			NP_597841.1
TANK	XM_047441820.1	c.-104+19381A>G		intron_variant			XP_047297776.1
TANK-AS1	NR_187173.1	n.231+2721T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TANK	ENST00000259075.6	c.-50+19381A>G		intron_variant		1		ENSP00000259075.2
TANK	ENST00000432002.5	c.-50+19381A>G		intron_variant		5		ENSP00000398157.1
TANK-AS1	ENST00000425470.1	n.165+2721T>C		intron_variant		3
TANK	ENST00000463502.1	n.98+19381A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0412 AC: 6267 AN: 152210 Hom.: 275 Cov.: 32

Gnomad AFR AF: 0.00904

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.0851

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0378

GnomAD4 exome AF: 0.0374 AC: 26412 AN: 706636 Hom.: 613 AF XY: 0.0372 AC XY: 12212 AN XY: 328688

Gnomad4 AFR exome AF: 0.00280

Gnomad4 AMR exome AF: 0.0412

Gnomad4 ASJ exome AF: 0.0187

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.0810

Gnomad4 FIN exome AF: 0.0650

Gnomad4 NFE exome AF: 0.0362

Gnomad4 OTH exome AF: 0.0472

GnomAD4 genome AF: 0.0412 AC: 6282 AN: 152328 Hom.: 278 Cov.: 32 AF XY: 0.0455 AC XY: 3388 AN XY: 74486

Gnomad4 AFR AF: 0.00902

Gnomad4 AMR AF: 0.0456

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.0855

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0372

Gnomad4 OTH AF: 0.0436

Alfa AF: 0.0353 Hom.: 18

Bravo AF: 0.0347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.83

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: rs3754974; hg19: chr2-162012955;