chr2-37733569-G-A

Variant names:

• chr2-37733569-G-A
• rs6733708
• ENST00000453555.1:c.-740+4790C>T

Variant summary

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

The ENST00000453555.1(CDC42EP3):​c.-740+4790C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 146,246 control chromosomes in the GnomAD database, including 13,849 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 0.41 (13849 hom., cov: 24)
• Consequence: CDC42EP3 ENST00000453555.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374465	XR_939971.3	n.170+3834C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42EP3	ENST00000453555.1	c.-740+4790C>T		intron_variant	Intron 1 of 3	3		ENSP00000398062.1
CDC42EP3-AS1	ENST00000751609.1	n.470-10883G>A		intron_variant	Intron 3 of 5
CDC42EP3-AS1	ENST00000751610.1	n.470-10883G>A		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.412 AC: 60257 AN: 146202 Hom.: 13835 Cov.: 24

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.0267

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.412 AC: 60296 AN: 146246 Hom.: 13849 Cov.: 24 AF XY: 0.408 AC XY: 28952 AN XY: 70940

African (AFR) AF: 0.599 AC: 23396 AN: 39088

American (AMR) AF: 0.340 AC: 5024 AN: 14770

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1460 AN: 3458

East Asian (EAS) AF: 0.0268 AC: 137 AN: 5114

South Asian (SAS) AF: 0.425 AC: 1948 AN: 4586

European-Finnish (FIN) AF: 0.339 AC: 3060 AN: 9026

Middle Eastern (MID) AF: 0.404 AC: 113 AN: 280

European-Non Finnish (NFE) AF: 0.357 AC: 23918 AN: 67014

Other (OTH) AF: 0.398 AC: 802 AN: 2014

Alfa AF: 0.378 Hom.: 14929

Bravo AF: 0.418

Asia WGS AF: 0.219 AC: 717 AN: 3282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.38
DANN	Benign	0.58
PhyloP100		-0.48

Splicing

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

Other links and lift over

dbSNP: rs6733708; hg19: chr2-37960712;