rs4242548

Positions:

Variant summary

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

The NM_014629.4(ARHGEF10):​c.3080-1436T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,130 control chromosomes in the GnomAD database, including 15,883 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 0.45 ( 15883 hom., cov: 34)

Consequence

ARHGEF10
NM_014629.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.387
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARHGEF10NM_014629.4 linkuse as main transcriptc.3080-1436T>C intron_variant ENST00000349830.8 NP_055444.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARHGEF10ENST00000349830.8 linkuse as main transcriptc.3080-1436T>C intron_variant 1 NM_014629.4 ENSP00000340297 P4O15013-5

Frequencies

GnomAD3 genomes
AF:
0.446
AC:
67854
AN:
152012
Hom.:
15867
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.346
Gnomad AMI
AF:
0.457
Gnomad AMR
AF:
0.433
Gnomad ASJ
AF:
0.469
Gnomad EAS
AF:
0.853
Gnomad SAS
AF:
0.571
Gnomad FIN
AF:
0.542
Gnomad MID
AF:
0.443
Gnomad NFE
AF:
0.455
Gnomad OTH
AF:
0.442
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.446
AC:
67906
AN:
152130
Hom.:
15883
Cov.:
34
AF XY:
0.456
AC XY:
33943
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.346
Gnomad4 AMR
AF:
0.432
Gnomad4 ASJ
AF:
0.469
Gnomad4 EAS
AF:
0.852
Gnomad4 SAS
AF:
0.571
Gnomad4 FIN
AF:
0.542
Gnomad4 NFE
AF:
0.455
Gnomad4 OTH
AF:
0.447
Alfa
AF:
0.455
Hom.:
15930
Bravo
AF:
0.434
Asia WGS
AF:
0.696
AC:
2420
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
1.9
DANN
Benign
0.66

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: rs4242548; hg19: chr8-1880530; API