Variant 19-7439985-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001367823.1(ARHGEF18):c.968-359T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000971 in 1,547,440 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00090 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00098 ( 4 hom. )

Consequence

ARHGEF18
NM_001367823.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0960

Variant links:

Genes affected

ARHGEF18 (HGNC:17090): (Rho/Rac guanine nucleotide exchange factor 18) Rho GTPases are GTP binding proteins that regulate a wide spectrum of cellular functions. These cellular processes include cytoskeletal rearrangements, gene transcription, cell growth and motility. Activation of Rho GTPases is under the direct control of guanine nucleotide exchange factors (GEFs). The protein encoded by this gene is a guanine nucleotide exchange factor and belongs to the Rho GTPase GEF family. Family members share a common feature, a Dbl (DH) homology domain followed by a pleckstrin (PH) homology domain. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Nov 2018]

ARHGEF18 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 19-7439985-T-A is Benign according to our data. Variant chr19-7439985-T-A is described in ClinVar as [Benign]. Clinvar id is 715866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-7439985-T-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0009 (137/152156) while in subpopulation NFE AF= 0.000912 (62/67978). AF 95% confidence interval is 0.00073. There are 2 homozygotes in gnomad4. There are 66 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF18	NM_001367823.1 linkuse as main transcript	c.968-359T>A		intron_variant		ENST00000668164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF18	ENST00000668164.2 linkuse as main transcript	c.968-359T>A		intron_variant			NM_001367823.1	A2	Q6ZSZ5-4

Frequencies

GnomAD3 genomes

AF:

0.000908

AC:

138

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000912

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00149

AC:

231

AN:

154608

Hom.:

AF XY:

0.00152

AC XY:

125

AN XY:

82100

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000663

Gnomad ASJ exome

AF:

0.0142

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000397

Gnomad FIN exome

AF:

0.0000598

Gnomad NFE exome

AF:

0.00127

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.000978

AC:

1365

AN:

1395284

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

738

AN XY:

687806

show subpopulations

Gnomad4 AFR exome

AF:

0.0000956

Gnomad4 AMR exome

AF:

0.000628

Gnomad4 ASJ exome

AF:

0.0146

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000443

Gnomad4 FIN exome

AF:

0.0000611

Gnomad4 NFE exome

AF:

0.000721

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.000900

AC:

137

AN:

152156

Hom.:

Cov.:

AF XY:

0.000887

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000912

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00244

Hom.:

Bravo

AF:

0.00106

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over