4-105567593-A-T

Variant names:

• chr4-105567593-A-T
• rs2903392
• NM_001242729.2:c.196+14632A>T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF38	NM_001242729.2	c.196+14632A>T		intron_variant	Intron 1 of 13	ENST00000420470.3	NP_001229658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF38	ENST00000420470.3	c.196+14632A>T		intron_variant	Intron 1 of 13	5	NM_001242729.2	ENSP00000416125.2
ARHGEF38	ENST00000265154.6	c.196+14632A>T		intron_variant	Intron 1 of 3	1		ENSP00000265154.2
ARHGEF38	ENST00000506828.1	n.69+14632A>T		intron_variant	Intron 1 of 3	5
ARHGEF38-IT1	ENST00000512262.1	n.122-2311A>T		intron_variant	Intron 2 of 2	3

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

Gnomad4 AFR AF: 0.976

Gnomad4 AMR AF: 0.963

Gnomad4 ASJ AF: 0.948

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.993

Gnomad4 FIN AF: 0.970

Gnomad4 NFE AF: 0.968

Gnomad4 OTH AF: 0.962

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.5
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs2903392; hg19: chr4-106488750;