rs7687176

Variant names:

• chr4-105605949-C-T
• rs7687176
• NM_001242729.2:c.385-7435C>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.385-7435C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.056 in 152,140 control chromosomes in the GnomAD database, including 264 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 0.056 (264 hom., cov: 32)
• Consequence: ARHGEF38 NM_001242729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF38	NM_001242729.2	c.385-7435C>T		intron_variant	Intron 2 of 13	ENST00000420470.3	NP_001229658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF38	ENST00000420470.3	c.385-7435C>T		intron_variant	Intron 2 of 13	5	NM_001242729.2	ENSP00000416125.2
ARHGEF38	ENST00000265154.6	c.385-7435C>T		intron_variant	Intron 2 of 3	1		ENSP00000265154.2
ARHGEF38	ENST00000506828.1	n.258-7435C>T		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8512 AN: 152022 Hom.: 263 Cov.: 32

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.0583

Gnomad EAS AF: 0.0332

Gnomad SAS AF: 0.0512

Gnomad FIN AF: 0.0440

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.0765

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

GnomAD4 genome AF: 0.0560 AC: 8517 AN: 152140 Hom.: 264 Cov.: 32 AF XY: 0.0562 AC XY: 4180 AN XY: 74392

African (AFR) AF: 0.0547 AC: 2272 AN: 41522

American (AMR) AF: 0.0721 AC: 1101 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0583 AC: 202 AN: 3466

East Asian (EAS) AF: 0.0329 AC: 170 AN: 5170

South Asian (SAS) AF: 0.0517 AC: 249 AN: 4818

European-Finnish (FIN) AF: 0.0440 AC: 466 AN: 10598

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0560 AC: 3804 AN: 67980

Other (OTH) AF: 0.0752 AC: 159 AN: 2114

Alfa AF: 0.0596 Hom.: 581

Bravo AF: 0.0592

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.54
PhyloP100		-1.9
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: rs7687176; hg19: chr4-106527106;