Variant 6-118465476-T-C 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_001042475.3(CEP85L):c.2347A>G(p.Ile783Val) variant causes a missense change. The variant allele was found at a frequency of 0.000349 in 1,613,710 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

CEP85L
NM_001042475.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.94

Variant links:

Genes affected

CEP85L (HGNC:21638): (centrosomal protein 85 like) The protein encoded by this gene was identified as a breast cancer antigen. Nothing more is known of its function at this time. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

CEP85L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058429837).

BP6

Variant 6-118465476-T-C is Benign according to our data. Variant chr6-118465476-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2395238.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 306 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP85L	NM_001042475.3 linkuse as main transcript	c.2347A>G	p.Ile783Val	missense_variant	13/13	ENST00000368491.8	NP_001035940.1	Q5SZL2-1Q3ZCQ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP85L	ENST00000368491.8 linkuse as main transcript	c.2347A>G	p.Ile783Val	missense_variant	13/13	1	NM_001042475.3	ENSP00000357477.3		Q5SZL2-1
CEP85L	ENST00000368488.9 linkuse as main transcript	c.2356A>G	p.Ile786Val	missense_variant	14/14	5		ENSP00000357474.5		Q5SZL2-4

Frequencies

GnomAD3 genomes

AF:

0.00200

AC:

304

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00705

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000453

AC:

113

AN:

249336

Hom.:

AF XY:

0.000333

AC XY:

AN XY:

135270

show subpopulations

Gnomad AFR exome

AF:

0.00652

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000176

AC:

257

AN:

1461414

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

106

AN XY:

727026

show subpopulations

Gnomad4 AFR exome

AF:

0.00658

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.00201

AC:

306

AN:

152296

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

146

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00707

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000346

Hom.:

Bravo

AF:

0.00232

ESP6500AA

AF:

0.00543

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000538

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0085

T;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.50

N;N

REVEL

Benign

0.15

Sift

Benign

0.23

T;T

Sift4G

Benign

0.35

T;T

Polyphen

1.0

D;.

Vest4

0.30

MVP

0.44

MPC

0.41

ClinPred

0.043

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.23

Splicing

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