rs1982346

chr4-105657597-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF38	NM_001242729.2	c.1234-1457A>G		intron_variant		ENST00000420470.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF38	ENST00000420470.3	c.1234-1457A>G		intron_variant		5	NM_001242729.2	P1
ARHGEF38	ENST00000508036.2	n.934-1457A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.0491

Gnomad4 AMR AF: 0.0825

Gnomad4 ASJ AF: 0.0654

Gnomad4 EAS AF: 0.0318

Gnomad4 SAS AF: 0.0498

Gnomad4 FIN AF: 0.0574

Gnomad4 NFE AF: 0.0762

Gnomad4 OTH AF: 0.0824

Alfa AF: 0.0687 Hom.: 123

Bravo AF: 0.0668

Asia WGS AF: 0.0440 AC: 152 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.37
Dann	Benign	0.88

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: rs1982346; hg19: chr4-106578754;