rs17035917

chr4-105599585-C-T

Variant summary

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

The NM_001242729.2(ARHGEF38):c.384+10150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 152,060 control chromosomes in the GnomAD database, including 566 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 0.079 (566 hom., cov: 32)
• Consequence: ARHGEF38 NM_001242729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF38	NM_001242729.2	c.384+10150C>T		intron_variant		ENST00000420470.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF38	ENST00000420470.3	c.384+10150C>T		intron_variant		5	NM_001242729.2	P1
ARHGEF38	ENST00000265154.6	c.384+10150C>T		intron_variant		1
ARHGEF38	ENST00000506828.1	n.257+10150C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11959 AN: 151942 Hom.: 564 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0212

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0628

Gnomad OTH AF: 0.0974

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

GnomAD4 genome AF: 0.0788 AC: 11982 AN: 152060 Hom.: 566 Cov.: 32 AF XY: 0.0762 AC XY: 5664 AN XY: 74350

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0754

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0212

Gnomad4 FIN AF: 0.0540

Gnomad4 NFE AF: 0.0628

Gnomad4 OTH AF: 0.0964

Alfa AF: 0.0679 Hom.: 589

Bravo AF: 0.0829

Asia WGS AF: 0.0240 AC: 83 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.3
Dann	Benign	0.66

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: rs17035917; hg19: chr4-106520742;