chr4-105610689-C-T

Variant names:

• chr4-105610689-C-T
• rs17035960
• NM_001242729.2:c.385-2695C>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.385-2695C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 151,976 control chromosomes in the GnomAD database, including 195 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 0.043 (195 hom., cov: 32)
• Consequence: ARHGEF38 NM_001242729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.97
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0603 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.385-2695C>T		intron	N/A	NP_001229658.1
	ARHGEF38	NM_017700.2		c.385-2695C>T		intron	N/A	NP_060170.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF38	ENST00000420470.3	TSL:5 MANE Select	c.385-2695C>T		intron	N/A	ENSP00000416125.2
	ARHGEF38	ENST00000265154.6	TSL:1	c.385-2695C>T		intron	N/A	ENSP00000265154.2
	ARHGEF38	ENST00000506828.1	TSL:5	n.258-2695C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6549 AN: 151858 Hom.: 196 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.0742

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0618

Gnomad OTH AF: 0.0668

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

GnomAD4 genome AF: 0.0430 AC: 6541 AN: 151976 Hom.: 195 Cov.: 32 AF XY: 0.0407 AC XY: 3026 AN XY: 74308

African (AFR) AF: 0.0107 AC: 442 AN: 41470

American (AMR) AF: 0.0630 AC: 960 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0742 AC: 257 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.0168 AC: 81 AN: 4808

European-Finnish (FIN) AF: 0.0284 AC: 301 AN: 10590

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0618 AC: 4200 AN: 67940

Other (OTH) AF: 0.0661 AC: 139 AN: 2102

Alfa AF: 0.0472 Hom.: 123

Bravo AF: 0.0452

Asia WGS AF: 0.0110 AC: 37 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.032
DANN	Benign	0.64
PhyloP100		-3.0
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: rs17035960; hg19: chr4-106531846;