rs2121558

Positions:

• chr4-105631576-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000265154.6(ARHGEF38):​c.*527A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 985,028 control chromosomes in the GnomAD database, including 33,058 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 0.32 (11123 hom., cov: 32)
  • Exomes 𝑓: 0.22 (21935 hom.)
• Consequence: ARHGEF38 ENST00000265154.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF38	NM_001242729.2	c.656+531A>T		intron_variant		ENST00000420470.3	NP_001229658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF38	ENST00000265154.6	c.*527A>T		3_prime_UTR_variant	4/4	1		ENSP00000265154
ARHGEF38	ENST00000420470.3	c.656+531A>T		intron_variant		5	NM_001242729.2	ENSP00000416125	P1
ARHGEF38	ENST00000506828.1	n.382-13612A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48915 AN: 151954 Hom.: 11088 Cov.: 32

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0924

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.219 AC: 182277 AN: 832956 Hom.: 21935 Cov.: 30 AF XY: 0.218 AC XY: 83831 AN XY: 384652

Gnomad4 AFR exome AF: 0.678

Gnomad4 AMR exome AF: 0.255

Gnomad4 ASJ exome AF: 0.322

Gnomad4 EAS exome AF: 0.0972

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.322 AC: 48996 AN: 152072 Hom.: 11123 Cov.: 32 AF XY: 0.313 AC XY: 23249 AN XY: 74356

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0924

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.335

Alfa AF: 0.263 Hom.: 945

Bravo AF: 0.353

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
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: rs2121558; hg19: chr4-106552733;