2-37713399-T-C

Variant names:

• chr2-37713399-T-C
• rs4670766
• ENST00000453555.1:c.-333+6139A>G

Variant summary

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

The ENST00000453555.1(CDC42EP3):​c.-333+6139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,118 control chromosomes in the GnomAD database, including 2,744 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 0.18 (2744 hom., cov: 32)
• Consequence: CDC42EP3 ENST00000453555.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738
• Publications: 11 publications found

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]

CDC42EP3-AS1 (HGNC:56370): (CDC42EP3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42EP3	ENST00000453555.1	c.-333+6139A>G		intron_variant	Intron 2 of 3	3		ENSP00000398062.1
CDC42EP3-AS1	ENST00000751609.1	n.470-31053T>C		intron_variant	Intron 3 of 5
CDC42EP3-AS1	ENST00000751610.1	n.470-31053T>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27413 AN: 152000 Hom.: 2735 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0267

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.180 AC: 27435 AN: 152118 Hom.: 2744 Cov.: 32 AF XY: 0.180 AC XY: 13373 AN XY: 74366

African (AFR) AF: 0.224 AC: 9308 AN: 41498

American (AMR) AF: 0.182 AC: 2781 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3470

East Asian (EAS) AF: 0.0268 AC: 139 AN: 5186

South Asian (SAS) AF: 0.342 AC: 1647 AN: 4814

European-Finnish (FIN) AF: 0.125 AC: 1318 AN: 10586

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11101 AN: 67960

Other (OTH) AF: 0.170 AC: 359 AN: 2110

Alfa AF: 0.163 Hom.: 9536

Bravo AF: 0.180

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.42
PhyloP100		0.74

Splicing

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

Other links and lift over

dbSNP: rs4670766; hg19: chr2-37940542;