4-105648653-C-T

Position:

• chr4-105648653-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001242729.2(ARHGEF38):​c.979C>T​(p.Leu327=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00469 in 1,531,282 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (6 hom., cov: 31)
  • Exomes 𝑓: 0.0047 (25 hom.)
• Consequence: ARHGEF38 NM_001242729.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.86

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 4-105648653-C-T is Benign according to our data. Variant chr4-105648653-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2655002.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF38	NM_001242729.2	c.979C>T	p.Leu327=	synonymous_variant	7/14	ENST00000420470.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF38	ENST00000420470.3	c.979C>T	p.Leu327=	synonymous_variant	7/14	5	NM_001242729.2	P1
ARHGEF38	ENST00000508036.2	n.679C>T		non_coding_transcript_exon_variant	4/10	5

Frequencies

GnomAD3 genomes AF: 0.00427 AC: 649 AN: 152152 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.00871

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00535

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00429 AC: 569 AN: 132638 Hom.: 5 AF XY: 0.00423 AC XY: 305 AN XY: 72160

Gnomad AFR exome AF: 0.000945

Gnomad AMR exome AF: 0.00434

Gnomad ASJ exome AF: 0.00845

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00476

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00511

Gnomad OTH exome AF: 0.00594

GnomAD4 exome AF: 0.00474 AC: 6533 AN: 1379012 Hom.: 25 Cov.: 30 AF XY: 0.00481 AC XY: 3272 AN XY: 680356

Gnomad4 AFR exome AF: 0.000796

Gnomad4 AMR exome AF: 0.00402

Gnomad4 ASJ exome AF: 0.00719

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00509

Gnomad4 FIN exome AF: 0.000475

Gnomad4 NFE exome AF: 0.00503

Gnomad4 OTH exome AF: 0.00557

GnomAD4 genome AF: 0.00426 AC: 649 AN: 152270 Hom.: 6 Cov.: 31 AF XY: 0.00438 AC XY: 326 AN XY: 74458

Gnomad4 AFR AF: 0.00116

Gnomad4 AMR AF: 0.00870

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00535

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00504 Hom.: 3

Bravo AF: 0.00478

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

ARHGEF38: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.4
DANN	Benign	0.65

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: rs138832734; hg19: chr4-106569810;