rs212389

Positions:

• chr6-159068759-G-A
• chr6-159068759-G-T

Variant summary

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

The XM_047419645.1(LOC112267968):​c.324-3821C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,054 control chromosomes in the GnomAD database, including 29,136 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 0.61 (29135 hom., cov: 32)
  • Exomes 𝑓: 0.63 (1 hom.)
• Consequence: LOC112267968 XM_047419645.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC112267968	XM_047419645.1	c.324-3821C>T		intron_variant			XP_047275601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAGAP-AS1	ENST00000646912.1	n.1263G>A		non_coding_transcript_exon_variant	4/5
ENSG00000285492	ENST00000642829.1	n.501-3821C>T		intron_variant
TAGAP-AS1	ENST00000643132.2	n.829-17794G>A		intron_variant
ENSG00000226032	ENST00000645980.1	n.96-3821C>T		intron_variant				ENSP00000520449.1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92222 AN: 151928 Hom.: 29117 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.624

GnomAD4 exome AF: 0.625 AC: 5 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 AFR exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.607 AC: 92267 AN: 152046 Hom.: 29135 Cov.: 32 AF XY: 0.619 AC XY: 45973 AN XY: 74320

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.718

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.903

Gnomad4 SAS AF: 0.753

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.628

Alfa AF: 0.609 Hom.: 6307

Bravo AF: 0.601

Asia WGS AF: 0.809 AC: 2813 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	5.1
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs212389; hg19: chr6-159489791;