rs17036052

Variant names:

• chr4-105642222-C-T
• rs17036052
• NM_001242729.2:c.675-2966C>T

Variant summary

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

The NM_001242729.2(ARHGEF38):​c.675-2966C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 152,188 control chromosomes in the GnomAD database, including 135 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 0.036 (135 hom., cov: 32)
• Consequence: ARHGEF38 NM_001242729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242729.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF38	NM_001242729.2	MANE Select	c.675-2966C>T		intron	N/A	NP_001229658.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF38	ENST00000420470.3	TSL:5 MANE Select	c.675-2966C>T		intron	N/A	ENSP00000416125.2
	ARHGEF38	ENST00000506828.1	TSL:5	n.382-2966C>T		intron	N/A
	ARHGEF38	ENST00000508036.2	TSL:5	n.375-2966C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5503 AN: 152070 Hom.: 135 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00953

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0511

Gnomad OTH AF: 0.0506

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

GnomAD4 genome AF: 0.0361 AC: 5499 AN: 152188 Hom.: 135 Cov.: 32 AF XY: 0.0342 AC XY: 2548 AN XY: 74400

African (AFR) AF: 0.0129 AC: 535 AN: 41530

American (AMR) AF: 0.0544 AC: 831 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00954 AC: 46 AN: 4822

European-Finnish (FIN) AF: 0.0207 AC: 219 AN: 10598

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0511 AC: 3477 AN: 67992

Other (OTH) AF: 0.0501 AC: 106 AN: 2116

Alfa AF: 0.0388 Hom.: 15

Bravo AF: 0.0388

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.50
PhyloP100		1.2
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: rs17036052; hg19: chr4-106563379;