Variant 1-197268441-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_201253.3(CRB1):c.29T>C(p.Leu10Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 1,613,214 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L10L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 1 hom. )

Consequence

CRB1
NM_201253.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 2.79

Variant links:

Genes affected

CRB1 (HGNC:2343): (crumbs cell polarity complex component 1) This gene encodes a protein which is similar to the Drosophila crumbs protein and localizes to the inner segment of mammalian photoreceptors. In Drosophila crumbs localizes to the stalk of the fly photoreceptor and may be a component of the molecular scaffold that controls proper development of polarity in the eye. Mutations in this gene are associated with a severe form of retinitis pigmentosa, RP12, and with Leber congenital amaurosis. Alternate splicing results in multiple transcript variants, some protein coding and some non-protein coding.[provided by RefSeq, Apr 2012]

CRB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033907562).

BP6

Variant 1-197268441-T-C is Benign according to our data. Variant chr1-197268441-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 546619.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRB1	NM_201253.3 linkuse as main transcript	c.29T>C	p.Leu10Pro	missense_variant	1/12	ENST00000367400.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRB1	ENST00000367400.8 linkuse as main transcript	c.29T>C	p.Leu10Pro	missense_variant	1/12	1	NM_201253.3	P1	P82279-1

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000394

AC:

AN:

251268

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00286

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000251

AC:

367

AN:

1460914

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

175

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00315

Gnomad4 NFE exome

AF:

0.000167

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000269

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000150

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000469

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2018

- -

Leber congenital amaurosis 8

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

May 18, 2021

- -

Retinitis pigmentosa 12;C3151202:Leber congenital amaurosis 8

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.087

BayesDel_noAF

Pathogenic

0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

.;.;T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.65

T;.;T;T

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.034

T;T;T;T

MetaSVM

Uncertain

0.56

MutationAssessor

Benign

1.9

L;L;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.4

N;.;N;N

REVEL

Pathogenic

0.72

Sift

Uncertain

0.023

D;.;D;D

Sift4G

Uncertain

0.0030

D;.;D;D

Polyphen

1.0

.;.;D;D

Vest4

0.81

MVP

0.90

MPC

0.20

ClinPred

0.081

GERP RS

5.1

Varity_R

0.71

gMVP

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

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