chr6-159093746-T-C

Variant names:

• chr6-159093746-T-C
• rs654690
• XM_047419645.1:c.323+1983A>G

Variant summary

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

The XM_047419645.1(LOC112267968):​c.323+1983A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,000 control chromosomes in the GnomAD database, including 44,822 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 0.76 (44822 hom., cov: 31)
• Consequence: LOC112267968 XM_047419645.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC112267968	XM_047419645.1	c.323+1983A>G		intron_variant	Intron 3 of 4		XP_047275601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285492	ENST00000642829.1	n.500+1983A>G		intron_variant	Intron 3 of 4
ENSG00000226032	ENST00000645980.1	n.95+1983A>G		intron_variant	Intron 1 of 6			ENSP00000520449.1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115376 AN: 151884 Hom.: 44758 Cov.: 31

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.748

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

GnomAD4 genome AF: 0.760 AC: 115499 AN: 152000 Hom.: 44822 Cov.: 31 AF XY: 0.766 AC XY: 56942 AN XY: 74306

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.932

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.743

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.750

Alfa AF: 0.683 Hom.: 24186

Bravo AF: 0.770

Asia WGS AF: 0.885 AC: 3078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs654690; hg19: chr6-159514778;