4-105672417-T-C

Variant names:

• chr4-105672417-T-C
• rs17036090
• NM_001242729.2:c.2148+4714T>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+4714T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 152,318 control chromosomes in the GnomAD database, including 225 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 0.050 (225 hom., cov: 32)
• Consequence: ARHGEF38 NM_001242729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF38	NM_001242729.2	c.2148+4714T>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+4714T>C		intron_variant	Intron 13 of 13	5	NM_001242729.2	ENSP00000416125.2

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7610 AN: 152200 Hom.: 226 Cov.: 32

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.0288

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0599

Gnomad OTH AF: 0.0702

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

GnomAD4 genome AF: 0.0499 AC: 7605 AN: 152318 Hom.: 225 Cov.: 32 AF XY: 0.0477 AC XY: 3555 AN XY: 74476

African (AFR) AF: 0.0373 AC: 1550 AN: 41580

American (AMR) AF: 0.0666 AC: 1018 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 254 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0186 AC: 90 AN: 4828

European-Finnish (FIN) AF: 0.0288 AC: 306 AN: 10608

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0599 AC: 4077 AN: 68024

Other (OTH) AF: 0.0695 AC: 147 AN: 2116

Alfa AF: 0.0519 Hom.: 35

Bravo AF: 0.0528

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.79
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism

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: rs17036090; hg19: chr4-106593574;