8-1892531-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014629.4(ARHGEF10):​c.1183-1038G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,884 control chromosomes in the GnomAD database, including 40,414 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 0.72 ( 40414 hom., cov: 30)

Consequence

ARHGEF10
NM_014629.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.32
Variant links:
Genes affected
ARHGEF10 (HGNC:14103): (Rho guanine nucleotide exchange factor 10) This gene encodes a Rho guanine nucleotide exchange factor (GEF). Rho GEFs regulate the activity of small Rho GTPases by stimulating the exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) and may play a role in neural morphogenesis. Mutations in this gene are associated with slowed nerve conduction velocity (SNCV). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARHGEF10NM_014629.4 linkc.1183-1038G>T intron_variant ENST00000349830.8 NP_055444.2 O15013-5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARHGEF10ENST00000349830.8 linkc.1183-1038G>T intron_variant 1 NM_014629.4 ENSP00000340297.3 O15013-5
KBTBD11-OT1ENST00000635855.1 linkn.*1137-1038G>T intron_variant 5 ENSP00000489726.1 A0A1B0GTJ5

Frequencies

GnomAD3 genomes
AF:
0.720
AC:
109198
AN:
151766
Hom.:
40357
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.852
Gnomad AMI
AF:
0.643
Gnomad AMR
AF:
0.732
Gnomad ASJ
AF:
0.526
Gnomad EAS
AF:
0.967
Gnomad SAS
AF:
0.775
Gnomad FIN
AF:
0.705
Gnomad MID
AF:
0.513
Gnomad NFE
AF:
0.629
Gnomad OTH
AF:
0.676
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.720
AC:
109318
AN:
151884
Hom.:
40414
Cov.:
30
AF XY:
0.726
AC XY:
53859
AN XY:
74214
show subpopulations
Gnomad4 AFR
AF:
0.852
Gnomad4 AMR
AF:
0.733
Gnomad4 ASJ
AF:
0.526
Gnomad4 EAS
AF:
0.967
Gnomad4 SAS
AF:
0.775
Gnomad4 FIN
AF:
0.705
Gnomad4 NFE
AF:
0.629
Gnomad4 OTH
AF:
0.680
Alfa
AF:
0.630
Hom.:
44396
Bravo
AF:
0.726
Asia WGS
AF:
0.882
AC:
3064
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.19
DANN
Benign
0.65

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.

Other links and lift over

dbSNP: rs4242520; hg19: chr8-1840697; API