rs13012266

Positions:

• chr2-37730337-T-C

Variant summary

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

The ENST00000453555.1(CDC42EP3):​c.-740+8022A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,134 control chromosomes in the GnomAD database, including 6,097 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 0.25 (6097 hom., cov: 32)
• Consequence: CDC42EP3 ENST00000453555.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

Genes affected

CDC42EP3 (HGNC:16943): (CDC42 effector protein 3) This gene encodes a member of a small family of guanosine triphosphate (GTP) metabolizing proteins that contain a CRIB (Cdc42, Rac interactive binding) domain. Members of this family of proteins act as effectors of CDC42 function. The encoded protein is involved in actin cytoskeleton re-organization during cell shape changes, including pseudopodia formation. A pseudogene of this gene is found on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

LOC105374465 (HGNC:):

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 = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105374465	XR_939971.3	n.170+7066A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42EP3	ENST00000453555.1	c.-740+8022A>G		intron_variant		3		ENSP00000398062.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38251 AN: 152016 Hom.: 6065 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0286

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.234

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.252 AC: 38341 AN: 152134 Hom.: 6097 Cov.: 32 AF XY: 0.249 AC XY: 18529 AN XY: 74416

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.0287

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.233

Alfa AF: 0.222 Hom.: 563

Bravo AF: 0.261

Asia WGS AF: 0.213 AC: 741 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13012266; hg19: chr2-37957480;