rs9295089

Positions:

• chr6-159042932-T-C

Variant summary

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

The NM_054114.5(TAGAP):​c.148+657A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,602 control chromosomes in the GnomAD database, including 4,422 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 0.19 (4419 hom., cov: 33)
  • Exomes 𝑓: 0.061 (3 hom.)
• Consequence: TAGAP NM_054114.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509

Genes affected

TAGAP (HGNC:15669): (T cell activation RhoGTPase activating protein) This gene encodes a member of the Rho GTPase-activator protein superfamily. The encoded protein may function as a Rho GTPase-activating protein. Alterations in this gene may be associated with several diseases, including rheumatoid arthritis, celiac disease, and multiple sclerosis. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2013]

TAGAP-AS1 (HGNC:55239): (TAGAP antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAGAP	NM_054114.5	c.148+657A>G		intron_variant		ENST00000367066.8
TAGAP-AS1	NR_183546.1	n.1972T>C		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAGAP	ENST00000367066.8	c.148+657A>G		intron_variant		1	NM_054114.5	P1
TAGAP-AS1	ENST00000646912.1	n.536+624T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28758 AN: 152126 Hom.: 4400 Cov.: 33

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.0947

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0823

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.0611 AC: 22 AN: 360 Hom.: 3 Cov.: 0 AF XY: 0.0539 AC XY: 11 AN XY: 204

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.0526

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0763

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.189 AC: 28824 AN: 152242 Hom.: 4419 Cov.: 33 AF XY: 0.183 AC XY: 13605 AN XY: 74454

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.0946

Gnomad4 ASJ AF: 0.0936

Gnomad4 EAS AF: 0.0326

Gnomad4 SAS AF: 0.0513

Gnomad4 FIN AF: 0.0823

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.151

Alfa AF: 0.120 Hom.: 2087

Bravo AF: 0.202

Asia WGS AF: 0.0580 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.50

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: rs9295089; hg19: chr6-159463964;