2-143435597-G-T

Position:

• chr2-143435597-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_018460.4(ARHGAP15):​c.475-4G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0071 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP15 NM_018460.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001113
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.112

Genes affected

ARHGAP15 (HGNC:21030): (Rho GTPase activating protein 15) RHO GTPases (see ARHA; MIM 165390) regulate diverse biologic processes, and their activity is regulated by RHO GTPase-activating proteins (GAPs), such as ARHGAP15 (Seoh et al., 2003 [PubMed 12650940]).[supplied by OMIM, Mar 2008]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 2-143435597-G-T is Benign according to our data. Variant chr2-143435597-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 774410.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP15	NM_018460.4	c.475-4G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000295095.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP15	ENST00000295095.11	c.475-4G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_018460.4	P1
	ENST00000546678.1	n.309-130137C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1701 AN: 44212 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.0280

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.0366

Gnomad NFE AF: 0.0502

Gnomad OTH AF: 0.0405

GnomAD3 exomes AF: 0.00611 AC: 305 AN: 49940 Hom.: 0 AF XY: 0.00568 AC XY: 149 AN XY: 26232

Gnomad AFR exome AF: 0.00225

Gnomad AMR exome AF: 0.0120

Gnomad ASJ exome AF: 0.0224

Gnomad EAS exome AF: 0.0122

Gnomad SAS exome AF: 0.00709

Gnomad FIN exome AF: 0.0103

Gnomad NFE exome AF: 0.00380

Gnomad OTH exome AF: 0.0126

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00710 AC: 5647 AN: 795812 Hom.: 1 Cov.: 32 AF XY: 0.00839 AC XY: 3253 AN XY: 387788

Gnomad4 AFR exome AF: 0.00304

Gnomad4 AMR exome AF: 0.0161

Gnomad4 ASJ exome AF: 0.0146

Gnomad4 EAS exome AF: 0.00513

Gnomad4 SAS exome AF: 0.0465

Gnomad4 FIN exome AF: 0.0144

Gnomad4 NFE exome AF: 0.00520

Gnomad4 OTH exome AF: 0.00834

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0385 AC: 1705 AN: 44240 Hom.: 0 Cov.: 0 AF XY: 0.0375 AC XY: 819 AN XY: 21818

Gnomad4 AFR AF: 0.0281

Gnomad4 AMR AF: 0.0279

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.0281

Gnomad4 SAS AF: 0.0362

Gnomad4 FIN AF: 0.0271

Gnomad4 NFE AF: 0.0502

Gnomad4 OTH AF: 0.0400

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.11
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000011
dbscSNV1_RF	Benign	0.016
SpliceAI score (max)		0.010		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: rs199653389; hg19: chr2-144193166;