rs4235415

Variant names:

• chr4-105672693-A-G
• rs4235415
• NM_001242729.2:c.2148+4990A>G

Variant summary

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

The NM_001242729.2(ARHGEF38):​c.2148+4990A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,150 control chromosomes in the GnomAD database, including 11,287 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 0.30 (11287 hom., cov: 32)
• Consequence: ARHGEF38 NM_001242729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF38	NM_001242729.2	c.2148+4990A>G		intron_variant	Intron 13 of 13	ENST00000420470.3	NP_001229658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF38	ENST00000420470.3	c.2148+4990A>G		intron_variant	Intron 13 of 13	5	NM_001242729.2	ENSP00000416125.2

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45037 AN: 152032 Hom.: 11257 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0745

Gnomad SAS AF: 0.0991

Gnomad FIN AF: 0.0558

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.296 AC: 45112 AN: 152150 Hom.: 11287 Cov.: 32 AF XY: 0.287 AC XY: 21319 AN XY: 74404

African (AFR) AF: 0.687 AC: 28467 AN: 41458

American (AMR) AF: 0.242 AC: 3704 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3470

East Asian (EAS) AF: 0.0744 AC: 386 AN: 5186

South Asian (SAS) AF: 0.0998 AC: 480 AN: 4810

European-Finnish (FIN) AF: 0.0558 AC: 593 AN: 10618

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9695 AN: 68008

Other (OTH) AF: 0.286 AC: 604 AN: 2110

Alfa AF: 0.199 Hom.: 7726

Bravo AF: 0.332

Asia WGS AF: 0.128 AC: 446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.37
DANN	Benign	0.39
PhyloP100		-0.19
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: rs4235415; hg19: chr4-106593850;