chr4-105672417-T-C

Position:

• chr4-105672417-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ARHGEF38	NM_001242729.2	c.2148+4714T>C		intron_variant		ENST00000420470.3	NP_001229658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF38	ENST00000420470.3	c.2148+4714T>C		intron_variant		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

Gnomad4 AFR AF: 0.0373

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.0732

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0186

Gnomad4 FIN AF: 0.0288

Gnomad4 NFE AF: 0.0599

Gnomad4 OTH AF: 0.0695

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

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: rs17036090; hg19: chr4-106593574;