chr4-105553818-C-A

Variant names:

• chr4-105553818-C-A
• rs2866799
• NM_001242729.2:c.196+857C>A

Variant summary

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

The NM_001242729.2(ARHGEF38):​c.196+857C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,084 control chromosomes in the GnomAD database, including 59,404 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 0.88 (59404 hom., cov: 31)
• Consequence: ARHGEF38 NM_001242729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF38	NM_001242729.2	c.196+857C>A		intron_variant	Intron 1 of 13	ENST00000420470.3	NP_001229658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF38	ENST00000420470.3	c.196+857C>A		intron_variant	Intron 1 of 13	5	NM_001242729.2	ENSP00000416125.2
ARHGEF38	ENST00000265154.6	c.196+857C>A		intron_variant	Intron 1 of 3	1		ENSP00000265154.2
ARHGEF38	ENST00000506828.1	n.69+857C>A		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133914 AN: 151966 Hom.: 59369 Cov.: 31

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.903

Gnomad OTH AF: 0.895

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

GnomAD4 genome AF: 0.881 AC: 134007 AN: 152084 Hom.: 59404 Cov.: 31 AF XY: 0.875 AC XY: 65034 AN XY: 74340

African (AFR) AF: 0.919 AC: 38135 AN: 41500

American (AMR) AF: 0.801 AC: 12227 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3105 AN: 3470

East Asian (EAS) AF: 0.595 AC: 3077 AN: 5170

South Asian (SAS) AF: 0.875 AC: 4202 AN: 4804

European-Finnish (FIN) AF: 0.843 AC: 8896 AN: 10558

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.903 AC: 61380 AN: 68004

Other (OTH) AF: 0.890 AC: 1879 AN: 2112

Alfa AF: 0.863 Hom.: 5630

Bravo AF: 0.877

Asia WGS AF: 0.737 AC: 2565 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.3
DANN	Benign	0.69
PhyloP100		-0.21
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: rs2866799; hg19: chr4-106474975;