Variant 6-110215286-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015891.3(CDC40):c.943C>G(p.Leu315Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00858 in 1,611,540 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0087 ( 74 hom. )

Consequence

CDC40
NM_015891.3 missense, splice_region

Scores

Splicing: ADA: 0.03779

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.35

Variant links:

Genes affected

CDC40 (HGNC:17350): (cell division cycle 40) Pre-mRNA splicing occurs in two sequential transesterification steps. The protein encoded by this gene is found to be essential for the catalytic step II in pre-mRNA splicing process. It is found in the spliceosome, and contains seven WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to yeast Prp17 protein, which functions in two different cellular processes: pre-mRNA splicing and cell cycle progression. It suggests that this protein may play a role in cell cycle progression. [provided by RefSeq, Jul 2008]

CDC40 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017160505).

BP6

Variant 6-110215286-C-G is Benign according to our data. Variant chr6-110215286-C-G is described in ClinVar as [Benign]. Clinvar id is 1695164.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1052 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC40	NM_015891.3 linkuse as main transcript	c.943C>G	p.Leu315Val	missense_variant, splice_region_variant	9/15	ENST00000307731.2
CDC40	XM_047418862.1 linkuse as main transcript	c.208C>G	p.Leu70Val	missense_variant, splice_region_variant	7/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CDC40	ENST00000307731.2 linkuse as main transcript	c.943C>G	p.Leu315Val	missense_variant, splice_region_variant	9/15	1	NM_015891.3	P1
CDC40	ENST00000368932.5 linkuse as main transcript	c.943C>G	p.Leu315Val	missense_variant, splice_region_variant	10/16	5		P1
CDC40	ENST00000368930.5 linkuse as main transcript	c.943C>G	p.Leu315Val	missense_variant, splice_region_variant	9/15	2
CDC40	ENST00000606893.5 linkuse as main transcript	n.2373C>G		splice_region_variant, non_coding_transcript_exon_variant	9/15	2

Frequencies

GnomAD3 genomes

AF:

0.00693

AC:

1054

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00865

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00709

AC:

1782

AN:

251278

Hom.:

AF XY:

0.00742

AC XY:

1008

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00501

Gnomad ASJ exome

AF:

0.0168

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00627

Gnomad FIN exome

AF:

0.00129

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00948

GnomAD4 exome

AF:

0.00875

AC:

12767

AN:

1459348

Hom.:

Cov.:

AF XY:

0.00883

AC XY:

6415

AN XY:

726110

show subpopulations

Gnomad4 AFR exome

AF:

0.00150

Gnomad4 AMR exome

AF:

0.00561

Gnomad4 ASJ exome

AF:

0.0162

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00639

Gnomad4 FIN exome

AF:

0.00140

Gnomad4 NFE exome

AF:

0.00973

Gnomad4 OTH exome

AF:

0.00882

GnomAD4 genome

AF:

0.00691

AC:

1052

AN:

152192

Hom.:

Cov.:

AF XY:

0.00681

AC XY:

507

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00864

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00236

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00729

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00988

AC:

ExAC

AF:

0.00686

AC:

833

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0105

EpiControl

AF:

0.0119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

CDC40: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

.;D;D

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.74

N;N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.26

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

0.80

P;P;.

Vest4

0.75

MVP

0.65

MPC

1.7

ClinPred

0.027

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.55

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.038

dbscSNV1_RF

Benign

0.41

SpliceAI score (max)

0.030

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