Variant 1-197347305-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_201253.3(CRB1):c.849-35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 1,595,734 control chromosomes in the GnomAD database, including 507,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 52274 hom., cov: 31)

Exomes 𝑓: 0.79 ( 454877 hom. )

Consequence

CRB1
NM_201253.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.140

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 1-197347305-T-C is Benign according to our data. Variant chr1-197347305-T-C is described in ClinVar as [Benign]. Clinvar id is 263260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRB1	NM_201253.3 linkuse as main transcript	c.849-35T>C		intron_variant		ENST00000367400.8	NP_957705.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRB1	ENST00000367400.8 linkuse as main transcript	c.849-35T>C		intron_variant		1	NM_201253.3	ENSP00000356370	P1	P82279-1

Frequencies

GnomAD3 genomes

AF:

0.827

AC:

125642

AN:

151988

Hom.:

52220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.907

Gnomad AMI

AF:

0.677

Gnomad AMR

AF:

0.825

Gnomad ASJ

AF:

0.799

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.884

Gnomad FIN

AF:

0.805

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.784

Gnomad OTH

AF:

0.832

GnomAD3 exomes

AF:

0.816

AC:

205112

AN:

251248

Hom.:

84049

AF XY:

0.818

AC XY:

111066

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.913

Gnomad AMR exome

AF:

0.836

Gnomad ASJ exome

AF:

0.803

Gnomad EAS exome

AF:

0.790

Gnomad SAS exome

AF:

0.886

Gnomad FIN exome

AF:

0.803

Gnomad NFE exome

AF:

0.786

Gnomad OTH exome

AF:

0.816

GnomAD4 exome

AF:

0.792

AC:

1144055

AN:

1443628

Hom.:

454877

Cov.:

AF XY:

0.795

AC XY:

571843

AN XY:

719466

show subpopulations

Gnomad4 AFR exome

AF:

0.917

Gnomad4 AMR exome

AF:

0.832

Gnomad4 ASJ exome

AF:

0.802

Gnomad4 EAS exome

AF:

0.789

Gnomad4 SAS exome

AF:

0.883

Gnomad4 FIN exome

AF:

0.802

Gnomad4 NFE exome

AF:

0.778

Gnomad4 OTH exome

AF:

0.811

GnomAD4 genome

AF:

0.827

AC:

125753

AN:

152106

Hom.:

52274

Cov.:

AF XY:

0.830

AC XY:

61677

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.907

Gnomad4 AMR

AF:

0.825

Gnomad4 ASJ

AF:

0.799

Gnomad4 EAS

AF:

0.778

Gnomad4 SAS

AF:

0.884

Gnomad4 FIN

AF:

0.805

Gnomad4 NFE

AF:

0.784

Gnomad4 OTH

AF:

0.834

Alfa

AF:

0.821

Hom.:

11497

Bravo

AF:

0.829

Asia WGS

AF:

0.841

AC:

2926

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Leber congenital amaurosis 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Retinitis pigmentosa 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Pigmented paravenous retinochoroidal atrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

9.0

DANN

Benign

0.72

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