ENST00000259075.6:c.-50+19381A>G

Variant names:

• chr2-161156444-A-G
• rs3754974
• ENST00000259075.6:c.-50+19381A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000259075.6(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 ENST00000259075.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342
• Publications: 1 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]

TANK-AS1 (HGNC:40575): (TANK antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000259075.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANK	NM_004180.3		c.-50+19381A>G		intron	N/A	NP_004171.2
	TANK	NM_133484.2		c.-50+19381A>G		intron	N/A	NP_597841.1
	TANK-AS1	NR_187173.1		n.231+2721T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANK	ENST00000259075.6	TSL:1	c.-50+19381A>G		intron	N/A	ENSP00000259075.2
	TANK	ENST00000432002.5	TSL:5	c.-50+19381A>G		intron	N/A	ENSP00000398157.1
	TANK-AS1	ENST00000425470.1	TSL:3	n.165+2721T>C		intron	N/A

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

African (AFR) AF: 0.00280 AC: 37 AN: 13192

American (AMR) AF: 0.0412 AC: 34 AN: 826

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 82 AN: 4388

East Asian (EAS) AF: 0.201 AC: 595 AN: 2960

South Asian (SAS) AF: 0.0810 AC: 1128 AN: 13930

European-Finnish (FIN) AF: 0.0650 AC: 13 AN: 200

Middle Eastern (MID) AF: 0.0249 AC: 34 AN: 1366

European-Non Finnish (NFE) AF: 0.0362 AC: 23395 AN: 646618

Other (OTH) AF: 0.0472 AC: 1094 AN: 23156

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

African (AFR) AF: 0.00902 AC: 375 AN: 41588

American (AMR) AF: 0.0456 AC: 698 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3470

East Asian (EAS) AF: 0.191 AC: 989 AN: 5186

South Asian (SAS) AF: 0.0855 AC: 413 AN: 4828

European-Finnish (FIN) AF: 0.104 AC: 1105 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0372 AC: 2532 AN: 68026

Other (OTH) AF: 0.0436 AC: 92 AN: 2112

Alfa AF: 0.0364 Hom.: 37

Bravo AF: 0.0347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.34
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: rs3754974; hg19: chr2-162012955;