rs2121558

Variant names:

• chr4-105631576-A-T
• rs2121558
• ENST00000265154.6:c.*527A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017700.2(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 NM_017700.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321
• Publications: 5 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 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017700.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF38	NM_001242729.2	MANE Select	c.656+531A>T		intron	N/A	NP_001229658.1
	ARHGEF38	NM_017700.2		c.*527A>T		3_prime_UTR	Exon 4 of 4	NP_060170.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF38	ENST00000265154.6	TSL:1	c.*527A>T		3_prime_UTR	Exon 4 of 4	ENSP00000265154.2
	ARHGEF38	ENST00000420470.3	TSL:5 MANE Select	c.656+531A>T		intron	N/A	ENSP00000416125.2
	ARHGEF38	ENST00000506828.1	TSL:5	n.382-13612A>T		intron	N/A

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

African (AFR) AF: 0.678 AC: 10705 AN: 15778

American (AMR) AF: 0.255 AC: 251 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1660 AN: 5152

East Asian (EAS) AF: 0.0972 AC: 353 AN: 3630

South Asian (SAS) AF: 0.154 AC: 2530 AN: 16458

European-Finnish (FIN) AF: 0.129 AC: 36 AN: 280

Middle Eastern (MID) AF: 0.297 AC: 481 AN: 1618

European-Non Finnish (NFE) AF: 0.210 AC: 160068 AN: 761766

Other (OTH) AF: 0.227 AC: 6193 AN: 27290

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

African (AFR) AF: 0.639 AC: 26474 AN: 41420

American (AMR) AF: 0.282 AC: 4315 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1076 AN: 3468

East Asian (EAS) AF: 0.101 AC: 525 AN: 5178

South Asian (SAS) AF: 0.135 AC: 651 AN: 4818

European-Finnish (FIN) AF: 0.0924 AC: 980 AN: 10608

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13885 AN: 67980

Other (OTH) AF: 0.335 AC: 706 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.65
PhyloP100		-0.32
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: rs2121558; hg19: chr4-106552733;