Variant X-63637882-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001353921.2(ARHGEF9):c.*146G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., 31 hem., cov: 19)

Exomes 𝑓: 0.0041 ( 1 hom. 83 hem. )

Consequence

ARHGEF9
NM_001353921.2 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.569

Variant links:

Genes affected

ARHGEF9 (HGNC:14561): (Cdc42 guanine nucleotide exchange factor 9) The protein encoded by this gene is a Rho-like GTPase that switches between the active (GTP-bound) state and inactive (GDP-bound) state to regulate CDC42 and other genes. This brain-specific protein also acts as an adaptor protein for the recruitment of gephyrin and together these proteins facilitate receceptor recruitement in GABAnergic and glycinergic synapses. Defects in this gene are the cause of startle disease with epilepsy (STHEE), also known as hyperekplexia with epilepsy, as well as several other types of cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ARHGEF9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant X-63637882-C-G is Benign according to our data. Variant chrX-63637882-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 633481.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00286 (240/83962) while in subpopulation AFR AF= 0.0102 (220/21601). AF 95% confidence interval is 0.00908. There are 1 homozygotes in gnomad4. There are 31 alleles in male gnomad4 subpopulation. Median coverage is 19. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 31 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF9	NM_001353921.2 linkuse as main transcript	c.*146G>C		3_prime_UTR_variant	10/10	ENST00000671741.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF9	ENST00000671741.2 linkuse as main transcript	c.*146G>C		3_prime_UTR_variant	10/10		NM_001353921.2	A1

Frequencies

GnomAD3 genomes

AF:

0.00286

AC:

240

AN:

83959

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

AN XY:

21325

show subpopulations

Gnomad AFR

AF:

0.0102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000824

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000510

Gnomad FIN

AF:

0.000763

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000211

Gnomad OTH

AF:

0.000923

GnomAD4 exome

AF:

0.00414

AC:

842

AN:

203368

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

AN XY:

59356

show subpopulations

Gnomad4 AFR exome

AF:

0.00495

Gnomad4 AMR exome

AF:

0.00969

Gnomad4 ASJ exome

AF:

0.00415

Gnomad4 EAS exome

AF:

0.00397

Gnomad4 SAS exome

AF:

0.00242

Gnomad4 FIN exome

AF:

0.00538

Gnomad4 NFE exome

AF:

0.00370

Gnomad4 OTH exome

AF:

0.00480

GnomAD4 genome

AF:

0.00286

AC:

240

AN:

83962

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

AN XY:

21342

show subpopulations

Gnomad4 AFR

AF:

0.0102

Gnomad4 AMR

AF:

0.000823

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000513

Gnomad4 FIN

AF:

0.000763

Gnomad4 NFE

AF:

0.000211

Gnomad4 OTH

AF:

0.000913

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Epilepsy

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital

Jul 26, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.025

DANN

Benign

0.39

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

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