7-27794316-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_006024.7(TAX1BP1):c.1411-7T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 1,600,970 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (52 hom.)
• Consequence: TAX1BP1 NM_006024.7 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.01077
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.302

Genes affected

TAX1BP1 (HGNC:11575): (Tax1 binding protein 1) This gene encodes a HTLV-1 tax1 binding protein. The encoded protein interacts with TNFAIP3, and inhibits TNF-induced apoptosis by mediating the TNFAIP3 anti-apoptotic activity. Degradation of this protein by caspase-3-like family proteins is associated with apoptosis induced by TNF. This protein may also have a role in the inhibition of inflammatory signaling pathways. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 7-27794316-T-G is Benign according to our data. Variant chr7-27794316-T-G is described in ClinVar as [Benign]. Clinvar id is 778298.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1668/152286) while in subpopulation AFR AF= 0.0362 (1506/41556). AF 95% confidence interval is 0.0347. There are 32 homozygotes in gnomad4. There are 811 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAX1BP1	NM_006024.7	c.1411-7T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000396319.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAX1BP1	ENST00000396319.7	c.1411-7T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006024.7

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1666 AN: 152168 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00383 AC: 940 AN: 245296 Hom.: 9 AF XY: 0.00304 AC XY: 403 AN XY: 132510

Gnomad AFR exome AF: 0.0388

Gnomad AMR exome AF: 0.00286

Gnomad ASJ exome AF: 0.000202

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00431

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000688

Gnomad OTH exome AF: 0.00320

GnomAD4 exome AF: 0.00184 AC: 2668 AN: 1448684 Hom.: 52 Cov.: 29 AF XY: 0.00183 AC XY: 1318 AN XY: 720348

Gnomad4 AFR exome AF: 0.0403

Gnomad4 AMR exome AF: 0.00324

Gnomad4 ASJ exome AF: 0.0000775

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00521

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000389

Gnomad4 OTH exome AF: 0.00387

GnomAD4 genome AF: 0.0110 AC: 1668 AN: 152286 Hom.: 32 Cov.: 32 AF XY: 0.0109 AC XY: 811 AN XY: 74472

Gnomad4 AFR AF: 0.0362

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00597 Hom.: 7

Bravo AF: 0.0126

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	9.5
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.011
dbscSNV1_RF	Benign	0.25
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: 34

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs115792581; hg19: chr7-27833935;