Genetic Variant ENST00000259075.6:c.-50+19381A>G (chr2-161156444-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.342

Publications

1 publications found

Variant links:

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 links:

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

TANK-AS1 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
TANK	NM_004180.3 link	c.-50+19381A>G	intron_variant	Intron 1 of 7	NP_004171.2	Q92844-1
TANK	NM_133484.2 link	c.-50+19381A>G	intron_variant	Intron 1 of 3	NP_597841.1	Q92844-3
TANK-AS1	NR_187173.1 link	n.231+2721T>C	intron_variant	Intron 2 of 2
TANK	XM_047441820.1 link	c.-104+19381A>G	intron_variant	Intron 1 of 8	XP_047297776.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
TANK	ENST00000259075.6 link	c.-50+19381A>G	intron_variant	Intron 1 of 7	1	ENSP00000259075.2	Q92844-1
TANK	ENST00000432002.5 link	c.-50+19381A>G	intron_variant	Intron 1 of 5	5	ENSP00000398157.1	E7EV32
TANK-AS1	ENST00000425470.1 link	n.165+2721T>C	intron_variant	Intron 2 of 2	3
TANK	ENST00000463502.1 link	n.98+19381A>G	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

6267

AN:

152210

Hom.:

275

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.00280

AC:

AN:

13192

American (AMR)

AF:

0.0412

AC:

AN:

826

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

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:

AN:

200

Middle Eastern (MID)

AF:

0.0249

AC:

AN:

1366

European-Non Finnish (NFE)

AF:

0.0362

AC:

23395

AN:

646618

Other (OTH)

AF:

0.0472

AC:

1094

AN:

23156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1178

2356

3534

4712

5890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1250

2500

3750

5000

6250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0412

AC:

6282

AN:

152328

Hom.:

278

Cov.:

AF XY:

0.0455

AC XY:

3388

AN XY:

74486

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0372

AC:

2532

AN:

68026

Other (OTH)

AF:

0.0436

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

295

590

886

1181

1476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0364

Hom.:

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

(source)

DANN

Benign

0.83

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over