4-105657597-A-G

Variant names:

• chr4-105657597-A-G
• rs1982346
• NM_001242729.2:c.1234-1457A>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.1234-1457A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 152,064 control chromosomes in the GnomAD database, including 340 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 0.066 (340 hom., cov: 32)
• Consequence: ARHGEF38 NM_001242729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0787 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF38	NM_001242729.2	MANE Select	c.1234-1457A>G		intron	N/A	NP_001229658.1	Q9NXL2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF38	ENST00000420470.3	TSL:5 MANE Select	c.1234-1457A>G		intron	N/A	ENSP00000416125.2	Q9NXL2-2
	ARHGEF38	ENST00000508036.2	TSL:5	n.934-1457A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0659 AC: 10008 AN: 151946 Hom.: 341 Cov.: 32

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0826

Gnomad ASJ AF: 0.0654

Gnomad EAS AF: 0.0321

Gnomad SAS AF: 0.0498

Gnomad FIN AF: 0.0574

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0762

Gnomad OTH AF: 0.0837

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

GnomAD4 genome AF: 0.0658 AC: 10012 AN: 152064 Hom.: 340 Cov.: 32 AF XY: 0.0650 AC XY: 4830 AN XY: 74336

African (AFR) AF: 0.0491 AC: 2037 AN: 41500

American (AMR) AF: 0.0825 AC: 1259 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0654 AC: 227 AN: 3470

East Asian (EAS) AF: 0.0318 AC: 165 AN: 5186

South Asian (SAS) AF: 0.0498 AC: 240 AN: 4818

European-Finnish (FIN) AF: 0.0574 AC: 605 AN: 10534

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0762 AC: 5178 AN: 67988

Other (OTH) AF: 0.0824 AC: 173 AN: 2100

Alfa AF: 0.0695 Hom.: 150

Bravo AF: 0.0668

Asia WGS AF: 0.0440 AC: 152 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.37
DANN	Benign	0.88
PhyloP100		0.27
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: rs1982346; hg19: chr4-106578754;