rs4709267

Positions:

• chr6-159035343-A-G

Variant summary

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

The NM_054114.5(TAGAP):​c.*484T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,640 control chromosomes in the GnomAD database, including 2,289 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 0.15 (2286 hom., cov: 32)
  • Exomes 𝑓: 0.086 (3 hom.)
• Consequence: TAGAP NM_054114.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAGAP	NM_054114.5	c.*484T>C		3_prime_UTR_variant	10/10	ENST00000367066.8	NP_473455.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAGAP	ENST00000367066	c.*484T>C		3_prime_UTR_variant	10/10	1	NM_054114.5	ENSP00000356033.4

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23117 AN: 152056 Hom.: 2285 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.0920

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.0858 AC: 40 AN: 466 Hom.: 3 Cov.: 0 AF XY: 0.100 AC XY: 24 AN XY: 240

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.0556

Gnomad4 NFE exome AF: 0.0719

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.152 AC: 23144 AN: 152174 Hom.: 2286 Cov.: 32 AF XY: 0.159 AC XY: 11840 AN XY: 74386

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.0920

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.161

Alfa AF: 0.114 Hom.: 829

Bravo AF: 0.169

Asia WGS AF: 0.278 AC: 966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.51

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: rs4709267; hg19: chr6-159456375;