rs7309

Positions:

• chr2-161236129-G-A

Variant summary

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

The NM_001199135.3(TANK):​c.*611G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 149,948 control chromosomes in the GnomAD database, including 14,328 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 0.43 (14327 hom., cov: 29)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: TANK NM_001199135.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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]

PSMD14-DT (HGNC:56104): (PSMD14 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TANK	NM_001199135.3	c.*611G>A		3_prime_UTR_variant	8/8	ENST00000392749.7	NP_001186064.1
PSMD14-DT	NR_110593.1	n.348+12395C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TANK	ENST00000392749.7	c.*611G>A		3_prime_UTR_variant	8/8	1	NM_001199135.3	ENSP00000376505	P1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 63945 AN: 149840 Hom.: 14323 Cov.: 29

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.406

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.425

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.427 AC: 63960 AN: 149946 Hom.: 14327 Cov.: 29 AF XY: 0.428 AC XY: 31292 AN XY: 73124

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.423

Alfa AF: 0.477 Hom.: 26928

Bravo AF: 0.430

Asia WGS AF: 0.415 AC: 1421 AN: 3422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.013
DANN	Benign	0.46

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: rs7309; hg19: chr2-162092640;