NM_001242729.2:c.384+10150C>T

Variant names:

• chr4-105599585-C-T
• rs17035917
• NM_001242729.2:c.384+10150C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242729.2(ARHGEF38):​c.384+10150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 152,060 control chromosomes in the GnomAD database, including 566 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 0.079 (566 hom., cov: 32)
• Consequence: ARHGEF38 NM_001242729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 12 publications found

Genes affected

ARHGEF38 (HGNC:25968): (Rho guanine nucleotide exchange factor 38) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ARHGEF38 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242729.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF38	NM_001242729.2	MANE Select	c.384+10150C>T		intron	N/A	NP_001229658.1
	ARHGEF38	NM_017700.2		c.384+10150C>T		intron	N/A	NP_060170.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF38	ENST00000420470.3	TSL:5 MANE Select	c.384+10150C>T		intron	N/A	ENSP00000416125.2
	ARHGEF38	ENST00000265154.6	TSL:1	c.384+10150C>T		intron	N/A	ENSP00000265154.2
	ARHGEF38	ENST00000506828.1	TSL:5	n.257+10150C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11959 AN: 151942 Hom.: 564 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0212

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0628

Gnomad OTH AF: 0.0974

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0788 AC: 11982 AN: 152060 Hom.: 566 Cov.: 32 AF XY: 0.0762 AC XY: 5664 AN XY: 74350

African (AFR) AF: 0.127 AC: 5260 AN: 41450

American (AMR) AF: 0.0754 AC: 1150 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0212 AC: 102 AN: 4814

European-Finnish (FIN) AF: 0.0540 AC: 571 AN: 10572

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0628 AC: 4270 AN: 67984

Other (OTH) AF: 0.0964 AC: 204 AN: 2116

Alfa AF: 0.0715 Hom.: 1061

Bravo AF: 0.0829

Asia WGS AF: 0.0240 AC: 83 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.3
DANN	Benign	0.66
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17035917; hg19: chr4-106520742;