rs6007334

chr22-44857631-A-Gchr22-44857631-A-T

Variant summary

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

The NM_181335.3(ARHGAP8):c.878-2100A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,000 control chromosomes in the GnomAD database, including 2,165 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 0.15 (2165 hom., cov: 32)
• Consequence: ARHGAP8 NM_181335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

Genes affected

ARHGAP8 (HGNC:677): (Rho GTPase activating protein 8) This gene encodes a member of the RHOGAP family. GAP (GTPase-activating) family proteins participate in signaling pathways that regulate cell processes involved in cytoskeletal changes. GAP proteins alternate between an active (GTP-bound) and inactive (GDP-bound) state based on the GTP:GDP ratio in the cell. This family member is a multidomain protein that functions to promote Erk activation and cell motility. Alternative splicing results in multiple transcript variants. Read-through transcripts from the upstream proline rich 5, renal (PRR5) gene into this gene also exist, which led to the original description of PRR5 and ARHGAP8 being a single gene. [provided by RefSeq, Nov 2010]

PRR5-ARHGAP8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP8	NM_181335.3	c.878-2100A>G		intron_variant		ENST00000356099.11
PRR5-ARHGAP8	NM_181334.6	c.1271-2100A>G		intron_variant
ARHGAP8	NM_001017526.2	c.971-2100A>G		intron_variant
ARHGAP8	NM_001198726.2	c.878-4644A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP8	ENST00000356099.11	c.878-2100A>G		intron_variant		1	NM_181335.3	P1
ARHGAP8	ENST00000336963.8	c.878-4644A>G		intron_variant		1
ARHGAP8	ENST00000389772.8	c.*703-2100A>G		intron_variant, NMD_transcript_variant		1
ARHGAP8	ENST00000389774.6	c.971-2100A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22530 AN: 151882 Hom.: 2158 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0819

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.149 AC: 22577 AN: 152000 Hom.: 2165 Cov.: 32 AF XY: 0.145 AC XY: 10761 AN XY: 74324

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.0816

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.0122

Gnomad4 SAS AF: 0.0715

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.116

Alfa AF: 0.131 Hom.: 203

Bravo AF: 0.152

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.5
Dann	Benign	0.81

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: rs6007334; hg19: chr22-45253511;