rs2866799

chr4-105553818-C-Achr4-105553818-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ARHGEF38	NM_001242729.2	c.196+857C>A		intron_variant		ENST00000420470.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF38	ENST00000420470.3	c.196+857C>A		intron_variant		5	NM_001242729.2	P1
ARHGEF38	ENST00000265154.6	c.196+857C>A		intron_variant		1
ARHGEF38	ENST00000506828.1	n.69+857C>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.919

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.903

Gnomad4 OTH AF: 0.890

Alfa AF: 0.860 Hom.: 5291

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

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

Other links and lift over

dbSNP: rs2866799; hg19: chr4-106474975;