4-105567593-A-T

Variant names:

• chr4-105567593-A-T
• rs2903392
• NM_001242729.2:c.196+14632A>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.196+14632A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 152,312 control chromosomes in the GnomAD database, including 71,786 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 0.97 (71786 hom., cov: 31)
• Consequence: ARHGEF38 NM_001242729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.799
• Publications: 0 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-IT1 (HGNC:41483): (ARHGEF38 intronic transcript 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.196+14632A>T		intron	N/A	NP_001229658.1
	ARHGEF38	NM_017700.2		c.196+14632A>T		intron	N/A	NP_060170.1
	ARHGEF38-IT1	NR_046840.1		n.122-2311A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF38	ENST00000420470.3	TSL:5 MANE Select	c.196+14632A>T		intron	N/A	ENSP00000416125.2
	ARHGEF38	ENST00000265154.6	TSL:1	c.196+14632A>T		intron	N/A	ENSP00000265154.2
	ARHGEF38	ENST00000506828.1	TSL:5	n.69+14632A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.971 AC: 147761 AN: 152194 Hom.: 71732 Cov.: 31

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.963

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.961

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

GnomAD4 genome AF: 0.971 AC: 147874 AN: 152312 Hom.: 71786 Cov.: 31 AF XY: 0.971 AC XY: 72305 AN XY: 74468

African (AFR) AF: 0.976 AC: 40576 AN: 41560

American (AMR) AF: 0.963 AC: 14721 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.948 AC: 3291 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5187 AN: 5188

South Asian (SAS) AF: 0.993 AC: 4798 AN: 4830

European-Finnish (FIN) AF: 0.970 AC: 10303 AN: 10620

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.968 AC: 65860 AN: 68034

Other (OTH) AF: 0.962 AC: 2031 AN: 2112

Alfa AF: 0.972 Hom.: 8920

Bravo AF: 0.970

Asia WGS AF: 0.992 AC: 3446 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.5
DANN	Benign	0.66
PhyloP100		0.80
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: rs2903392; hg19: chr4-106488750;