chr4-105596842-C-G

Variant names:

• chr4-105596842-C-G
• rs10516519
• NM_001242729.2:c.384+7407C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242729.2(ARHGEF38):​c.384+7407C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,104 control chromosomes in the GnomAD database, including 5,724 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 0.26 (5724 hom., cov: 32)
• Consequence: ARHGEF38 NM_001242729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF38	NM_001242729.2	c.384+7407C>G		intron_variant	Intron 2 of 13	ENST00000420470.3	NP_001229658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF38	ENST00000420470.3	c.384+7407C>G		intron_variant	Intron 2 of 13	5	NM_001242729.2	ENSP00000416125.2
ARHGEF38	ENST00000265154.6	c.384+7407C>G		intron_variant	Intron 2 of 3	1		ENSP00000265154.2
ARHGEF38	ENST00000506828.1	n.257+7407C>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39342 AN: 151986 Hom.: 5697 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0538

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.259 AC: 39409 AN: 152104 Hom.: 5724 Cov.: 32 AF XY: 0.254 AC XY: 18849 AN XY: 74352

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.0536

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.269

Alfa AF: 0.252 Hom.: 694

Bravo AF: 0.263

Asia WGS AF: 0.121 AC: 421 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.097
DANN	Benign	0.57

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: rs10516519; hg19: chr4-106517999;