NM_173728.4:c.61delC

Variant names:

• chr17-8312098-TC-T
• NM_173728.4:c.61delC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_173728.4(ARHGEF15):​c.61delC​(p.Arg21AlafsTer161) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 989,850 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R21R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: ARHGEF15 NM_173728.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0890
• Publications: 0 publications found

Genes affected

ARHGEF15 (HGNC:15590): (Rho guanine nucleotide exchange factor 15) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein-coupled receptors. This gene encodes a protein that functions as a specific guanine nucleotide exchange factor for RhoA. It also interacts with ephrin A4 in vascular smooth muscle cells. Two alternatively spliced transcripts variants that encode the same protein have been found for this gene. [provided by RefSeq, Aug 2010]

ARHGEF15 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000226871 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 10 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173728.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF15	NM_173728.4	MANE Select	c.61delC	p.Arg21AlafsTer161	frameshift	Exon 2 of 16	NP_776089.2
	ARHGEF15	NM_025014.2		c.61delC	p.Arg21AlafsTer161	frameshift	Exon 2 of 16	NP_079290.1	O94989

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF15	ENST00000361926.8	TSL:1 MANE Select	c.61delC	p.Arg21AlafsTer161	frameshift	Exon 2 of 16	ENSP00000355026.3	O94989
	ARHGEF15	ENST00000421050.2	TSL:1	c.61delC	p.Arg21AlafsTer161	frameshift	Exon 2 of 16	ENSP00000412505.1	O94989
	ARHGEF15	ENST00000852584.1		c.61delC	p.Arg21AlafsTer161	frameshift	Exon 2 of 16	ENSP00000522643.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.0000101 AC: 10 AN: 989850 Hom.: 0 Cov.: 36 AF XY: 0.0000145 AC XY: 7 AN XY: 482910

African (AFR) AF: 0.00 AC: 0 AN: 19894

American (AMR) AF: 0.00 AC: 0 AN: 22862

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11536

East Asian (EAS) AF: 0.00 AC: 0 AN: 13764

South Asian (SAS) AF: 0.00 AC: 0 AN: 46808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3790

European-Non Finnish (NFE) AF: 0.0000124 AC: 10 AN: 807188

Other (OTH) AF: 0.00 AC: 0 AN: 34834

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Developmental and epileptic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.089

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

Other links and lift over

hg19: chr17-8215416;