rs139300908

Variant names:

• chr19-54465162-G-A
• rs139300908
• NM_145057.4:c.386C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-54465162-G-A
• chr19-54465162-G-C
• chr19-54465162-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_145057.4(CDC42EP5):​c.386C>T​(p.Pro129Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000995 in 1,412,152 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P129R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0010 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (35 hom.)
• Consequence: CDC42EP5 NM_145057.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.785
• Publications: 2 publications found

Genes affected

CDC42EP5 (HGNC:17408): (CDC42 effector protein 5) Cell division control protein 42 (CDC42), a small Rho GTPase, regulates the formation of F-actin-containing structures through its interaction with the downstream effector proteins. The protein encoded by this gene is a member of the Borg (binder of Rho GTPases) family of CDC42 effector proteins. Borg family proteins contain a CRIB (Cdc42/Rac interactive-binding) domain. They bind to CDC42 and regulate its function negatively. The encoded protein may inhibit c-Jun N-terminal kinase (JNK) independently of CDC42 binding. The protein may also play a role in septin organization and inducing pseudopodia formation in fibroblasts [provided by RefSeq, Jul 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019887388).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000999 (152/152164) while in subpopulation EAS AF = 0.0264 (136/5154). AF 95% confidence interval is 0.0228. There are 3 homozygotes in GnomAd4. There are 81 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC42EP5	NM_145057.4	c.386C>T	p.Pro129Leu	missense_variant	Exon 3 of 3	ENST00000301200.3	NP_659494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42EP5	ENST00000301200.3	c.386C>T	p.Pro129Leu	missense_variant	Exon 3 of 3	1	NM_145057.4	ENSP00000301200.2

Frequencies

GnomAD3 genomes AF: 0.000973 AC: 148 AN: 152056 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0261

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00210 AC: 85 AN: 40536 AF XY: 0.00165

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000520

Gnomad EAS exome AF: 0.0393

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000942

GnomAD4 exome AF: 0.000994 AC: 1253 AN: 1259988 Hom.: 35 Cov.: 31 AF XY: 0.000939 AC XY: 580 AN XY: 617720

African (AFR) AF: 0.0000398 AC: 1 AN: 25120

American (AMR) AF: 0.000134 AC: 2 AN: 14968

Ashkenazi Jewish (ASJ) AF: 0.000108 AC: 2 AN: 18434

East Asian (EAS) AF: 0.0400 AC: 1151 AN: 28774

South Asian (SAS) AF: 0.0000501 AC: 3 AN: 59846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4670

European-Non Finnish (NFE) AF: 0.00000684 AC: 7 AN: 1023024

Other (OTH) AF: 0.00168 AC: 87 AN: 51812

GnomAD4 genome AF: 0.000999 AC: 152 AN: 152164 Hom.: 3 Cov.: 32 AF XY: 0.00109 AC XY: 81 AN XY: 74390

African (AFR) AF: 0.0000722 AC: 3 AN: 41554

American (AMR) AF: 0.000457 AC: 7 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0264 AC: 136 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67966

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000922

ExAC AF: 0.00153 AC: 157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.56
DANN	Benign	0.96
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.11	N
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.79
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.028
Sift	Benign	0.17	T
Sift4G	Benign	0.076	T
Polyphen		0.016	B
Vest4		0.12
MVP		0.21
MPC		0.89
ClinPred		0.0090	T
GERP RS		-1.1
Varity_R		0.062
gMVP		0.19
Mutation Taster		=99/1	polymorphism

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: rs139300908; hg19: chr19-54976346; COSMIC: COSV100002689; COSMIC: COSV100002689;