17-73285213-A-G

Variant names:

• chr17-73285213-A-G
• rs3751928
• NM_012121.5:c.*217T>C

Variant summary

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

The ENST00000335793.4(CDC42EP4):​c.*217T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 439,882 control chromosomes in the GnomAD database, including 67,365 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 0.55 (22755 hom., cov: 33)
  • Exomes 𝑓: 0.55 (44610 hom.)
• Consequence: CDC42EP4 ENST00000335793.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• Publications: 9 publications found

Genes affected

CDC42EP4 (HGNC:17147): (CDC42 effector protein 4) The product of this gene is a member of the CDC42-binding protein family. Members of this family interact with Rho family GTPases and regulate the organization of the actin cytoskeleton. This protein has been shown to bind both CDC42 and TC10 GTPases in a GTP-dependent manner. When overexpressed in fibroblasts, this protein was able to induce pseudopodia formation, which suggested a role in inducing actin filament assembly and cell shape control. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000335793.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42EP4	NM_012121.5	MANE Select	c.*217T>C		3_prime_UTR	Exon 2 of 2	NP_036253.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42EP4	ENST00000335793.4	TSL:1 MANE Select	c.*217T>C		3_prime_UTR	Exon 2 of 2	ENSP00000338258.3
	CDC42EP4	ENST00000439510.2	TSL:2	c.*217T>C		3_prime_UTR	Exon 3 of 3	ENSP00000404270.2
	CDC42EP4	ENST00000581014.1	TSL:5	c.*245T>C		3_prime_UTR	Exon 3 of 3	ENSP00000464104.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83108 AN: 151944 Hom.: 22738 Cov.: 33

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.552 AC: 159019 AN: 287820 Hom.: 44610 Cov.: 3 AF XY: 0.553 AC XY: 81452 AN XY: 147176

African (AFR) AF: 0.498 AC: 4508 AN: 9060

American (AMR) AF: 0.570 AC: 6554 AN: 11494

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 5325 AN: 10010

East Asian (EAS) AF: 0.590 AC: 14502 AN: 24570

South Asian (SAS) AF: 0.598 AC: 7624 AN: 12746

European-Finnish (FIN) AF: 0.601 AC: 12737 AN: 21182

Middle Eastern (MID) AF: 0.515 AC: 743 AN: 1444

European-Non Finnish (NFE) AF: 0.542 AC: 97103 AN: 179166

Other (OTH) AF: 0.547 AC: 9923 AN: 18148

GnomAD4 genome AF: 0.547 AC: 83165 AN: 152062 Hom.: 22755 Cov.: 33 AF XY: 0.554 AC XY: 41203 AN XY: 74328

African (AFR) AF: 0.503 AC: 20883 AN: 41490

American (AMR) AF: 0.578 AC: 8830 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1857 AN: 3472

East Asian (EAS) AF: 0.610 AC: 3141 AN: 5148

South Asian (SAS) AF: 0.610 AC: 2939 AN: 4818

European-Finnish (FIN) AF: 0.618 AC: 6539 AN: 10584

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37185 AN: 67946

Other (OTH) AF: 0.530 AC: 1121 AN: 2114

Alfa AF: 0.539 Hom.: 45778

Bravo AF: 0.537

Asia WGS AF: 0.603 AC: 2101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.25
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3751928; hg19: chr17-71281352;