Variant 3-45091380-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022842.5(CDCP1):c.1786G>A(p.Gly596Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,614,134 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 20 hom. )

Consequence

CDCP1
NM_022842.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.19

Variant links:

Genes affected

CDCP1 (HGNC:24357): (CUB domain containing protein 1) This gene encodes a transmembrane protein which contains three extracellular CUB domains and acts as a substrate for Src family kinases. The protein plays a role in the tyrosine phosphorylation-dependent regulation of cellular events that are involved in tumor invasion and metastasis. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

CDCP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007077962).

BP6

Variant 3-45091380-C-T is Benign according to our data. Variant chr3-45091380-C-T is described in ClinVar as [Benign]. Clinvar id is 712052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1599/152282) while in subpopulation AFR AF= 0.0351 (1459/41538). AF 95% confidence interval is 0.0336. There are 23 homozygotes in gnomad4. There are 733 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDCP1	NM_022842.5 linkuse as main transcript	c.1786G>A	p.Gly596Ser	missense_variant	7/9	ENST00000296129.6	NP_073753.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDCP1	ENST00000296129.6 linkuse as main transcript	c.1786G>A	p.Gly596Ser	missense_variant	7/9	1	NM_022842.5	ENSP00000296129	P1	Q9H5V8-1

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1589

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0350

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00297

AC:

745

AN:

251208

Hom.:

AF XY:

0.00208

AC XY:

283

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.0351

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000493

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00140

AC:

2052

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

900

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0345

Gnomad4 AMR exome

AF:

0.00313

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000452

Gnomad4 OTH exome

AF:

0.00313

GnomAD4 genome

AF:

0.0105

AC:

1599

AN:

152282

Hom.:

Cov.:

AF XY:

0.00984

AC XY:

733

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0351

Gnomad4 AMR

AF:

0.00529

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.00258

Hom.:

Bravo

AF:

0.0120

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0309

AC:

136

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00354

AC:

430

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 24, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0071

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

0.76

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.2

REVEL

Benign

0.16

Sift

Benign

0.10

Sift4G

Uncertain

0.035

Polyphen

1.0

Vest4

0.34

MVP

0.41

MPC

0.98

ClinPred

0.044

GERP RS

4.3

Varity_R

0.057

gMVP

0.76

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over