2-37733470-A-T

Variant names:

• chr2-37733470-A-T
• rs17511102
• ENST00000453555.1:c.-740+4889T>A

Variant summary

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

The ENST00000453555.1(CDC42EP3):​c.-740+4889T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.056 in 152,162 control chromosomes in the GnomAD database, including 331 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 0.056 (331 hom., cov: 31)
• Consequence: CDC42EP3 ENST00000453555.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 50 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)

LOC105374465 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.085 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374465	XR_939971.3	n.170+3933T>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42EP3	ENST00000453555.1	c.-740+4889T>A		intron_variant	Intron 1 of 3	3		ENSP00000398062.1
CDC42EP3-AS1	ENST00000751609.1	n.470-10982A>T		intron_variant	Intron 3 of 5
CDC42EP3-AS1	ENST00000751610.1	n.470-10982A>T		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8517 AN: 152044 Hom.: 331 Cov.: 31

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.0410

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0868

Gnomad OTH AF: 0.0574

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

GnomAD4 genome AF: 0.0560 AC: 8516 AN: 152162 Hom.: 331 Cov.: 31 AF XY: 0.0543 AC XY: 4037 AN XY: 74402

African (AFR) AF: 0.0190 AC: 788 AN: 41526

American (AMR) AF: 0.0409 AC: 625 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 127 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0139 AC: 67 AN: 4820

European-Finnish (FIN) AF: 0.0682 AC: 721 AN: 10572

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0869 AC: 5906 AN: 67998

Other (OTH) AF: 0.0568 AC: 120 AN: 2112

Alfa AF: 0.0352 Hom.: 12

Bravo AF: 0.0522

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs17511102; hg19: chr2-37960613;