rs6733708

Variant names:

• chr2-37733569-G-A
• rs6733708
• ENST00000956783.1:c.-531+3834C>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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000453555.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42EP3	ENST00000956783.1		c.-531+3834C>T		intron	N/A	ENSP00000626842.1
	CDC42EP3	ENST00000956784.1		c.-685+3834C>T		intron	N/A	ENSP00000626843.1
	CDC42EP3	ENST00000956785.1		c.-844+3834C>T		intron	N/A	ENSP00000626844.1

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6733708;

hg19: chr2-37960712;