4-105671460-G-C

Variant names:

• chr4-105671460-G-C
• rs12512339
• NM_001242729.2:c.2148+3757G>C

Variant summary

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

The NM_001242729.2(ARHGEF38):​c.2148+3757G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,150 control chromosomes in the GnomAD database, including 38,432 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 0.67 (38432 hom., cov: 32)
• Consequence: ARHGEF38 NM_001242729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF38	NM_001242729.2	c.2148+3757G>C		intron_variant	Intron 13 of 13	ENST00000420470.3	NP_001229658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF38	ENST00000420470.3	c.2148+3757G>C		intron_variant	Intron 13 of 13	5	NM_001242729.2	ENSP00000416125.2

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102402 AN: 152032 Hom.: 38419 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.673 AC: 102446 AN: 152150 Hom.: 38432 Cov.: 32 AF XY: 0.684 AC XY: 50915 AN XY: 74404

African (AFR) AF: 0.312 AC: 12954 AN: 41466

American (AMR) AF: 0.732 AC: 11195 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2473 AN: 3472

East Asian (EAS) AF: 0.924 AC: 4788 AN: 5180

South Asian (SAS) AF: 0.852 AC: 4114 AN: 4828

European-Finnish (FIN) AF: 0.924 AC: 9804 AN: 10610

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54779 AN: 67990

Other (OTH) AF: 0.692 AC: 1463 AN: 2114

Alfa AF: 0.731 Hom.: 5361

Bravo AF: 0.640

Asia WGS AF: 0.859 AC: 2989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.75
PhyloP100		0.35
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: rs12512339; hg19: chr4-106592617;