NM_001353921.2:c.*176_*181delCACACA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_001353921.2(ARHGEF9):​c.*176_*181delCACACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 308,742 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 81 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., 53 hem., cov: 12)
Exomes 𝑓: 0.0023 ( 0 hom. 28 hem. )

Consequence

ARHGEF9
NM_001353921.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.64
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00226 (478/211726) while in subpopulation AFR AF= 0.0278 (177/6378). AF 95% confidence interval is 0.0244. There are 0 homozygotes in gnomad4_exome. There are 28 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 53 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGEF9NM_001353921.2 linkc.*176_*181delCACACA 3_prime_UTR_variant Exon 10 of 10 ENST00000671741.2 NP_001340850.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGEF9ENST00000671741 linkc.*176_*181delCACACA 3_prime_UTR_variant Exon 10 of 10 NM_001353921.2 ENSP00000500715.1 A0A5F9ZHY9

Frequencies

GnomAD3 genomes
AF:
0.00222
AC:
215
AN:
97004
Hom.:
0
Cov.:
12
AF XY:
0.00215
AC XY:
51
AN XY:
23748
show subpopulations
Gnomad AFR
AF:
0.00641
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000799
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000318
Gnomad SAS
AF:
0.00142
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00966
Gnomad NFE
AF:
0.000706
Gnomad OTH
AF:
0.00233
GnomAD4 exome
AF:
0.00226
AC:
478
AN:
211726
Hom.:
0
AF XY:
0.000448
AC XY:
28
AN XY:
62522
show subpopulations
Gnomad4 AFR exome
AF:
0.0278
Gnomad4 AMR exome
AF:
0.00171
Gnomad4 ASJ exome
AF:
0.00118
Gnomad4 EAS exome
AF:
0.000755
Gnomad4 SAS exome
AF:
0.00226
Gnomad4 FIN exome
AF:
0.00122
Gnomad4 NFE exome
AF:
0.00125
Gnomad4 OTH exome
AF:
0.00439
GnomAD4 genome
AF:
0.00227
AC:
220
AN:
97016
Hom.:
0
Cov.:
12
AF XY:
0.00223
AC XY:
53
AN XY:
23770
show subpopulations
Gnomad4 AFR
AF:
0.00656
Gnomad4 AMR
AF:
0.000798
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000319
Gnomad4 SAS
AF:
0.00144
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000707
Gnomad4 OTH
AF:
0.00307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs10542660; hg19: chrX-62857726; API