6-159069404-C-T

Position:

• chr6-159069404-C-T

Variant summary

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

The XM_047419645.1(LOC112267968):​c.324-4466G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,010 control chromosomes in the GnomAD database, including 20,323 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 0.50 (20323 hom., cov: 31)
• Consequence: LOC112267968 XM_047419645.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247

Genes affected

LOC112267968 (HGNC:):

ENSG00000226032 (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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC112267968	XM_047419645.1	c.324-4466G>A		intron_variant			XP_047275601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000285492	ENST00000642829.1	n.501-4466G>A		intron_variant
TAGAP-AS1	ENST00000643132.2	n.829-17149C>T		intron_variant
ENSG00000226032	ENST00000645980.1	n.96-4466G>A		intron_variant				ENSP00000520449.1
TAGAP-AS1	ENST00000646912.1	n.1606+302C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75918 AN: 151890 Hom.: 20322 Cov.: 31

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.503

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.499 AC: 75925 AN: 152010 Hom.: 20323 Cov.: 31 AF XY: 0.502 AC XY: 37305 AN XY: 74314

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.499

Alfa AF: 0.573 Hom.: 50157

Bravo AF: 0.469

Asia WGS AF: 0.494 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.73
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs212388; hg19: chr6-159490436;