rs1738074

Positions:

• chr6-159044945-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.-125A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 398,082 control chromosomes in the GnomAD database, including 56,700 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 0.49 (19585 hom., cov: 30)
  • Exomes 𝑓: 0.54 (37115 hom.)
• Consequence: TAGAP NM_054114.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.70

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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAGAP	NM_054114.5	c.-125A>G		5_prime_UTR_variant	1/10	ENST00000367066.8	NP_473455.2
TAGAP	NM_138810.4	c.-125A>G		5_prime_UTR_variant	1/8		NP_620165.1
TAGAP	NM_152133.3	c.-492A>G		5_prime_UTR_variant	1/9		NP_687034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAGAP	ENST00000367066.8	c.-125A>G		5_prime_UTR_variant	1/10	1	NM_054114.5	ENSP00000356033	P1
TAGAP-AS1	ENST00000646912.1	n.536+2637T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74904 AN: 151630 Hom.: 19589 Cov.: 30

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.508

GnomAD4 exome AF: 0.540 AC: 133082 AN: 246332 Hom.: 37115 Cov.: 0 AF XY: 0.543 AC XY: 67846 AN XY: 124852

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.579

Gnomad4 EAS exome AF: 0.321

Gnomad4 SAS exome AF: 0.617

Gnomad4 FIN exome AF: 0.574

Gnomad4 NFE exome AF: 0.582

Gnomad4 OTH exome AF: 0.525

GnomAD4 genome AF: 0.494 AC: 74919 AN: 151750 Hom.: 19585 Cov.: 30 AF XY: 0.497 AC XY: 36827 AN XY: 74142

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.507

Alfa AF: 0.563 Hom.: 56130

Bravo AF: 0.470

Asia WGS AF: 0.547 AC: 1901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.76

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: rs1738074; hg19: chr6-159465977; COSMIC: COSV57850964; COSMIC: COSV57850964;