1-197347305-T-C

Position:

• chr1-197347305-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.140

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 (HGNC:):

ACMG classification

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	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	c.849-35T>C		intron_variant		1	NM_201253.3	ENSP00000356370.3

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125642 AN: 151988 Hom.: 52220 Cov.: 31

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

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.: 27 AF XY: 0.795 AC XY: 571843 AN XY: 719466

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.: 31 AF XY: 0.830 AC XY: 61677 AN XY: 74338

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

Submissions by phenotype

not provided Benign:2

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

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

Other links and lift over

dbSNP: rs1337167; hg19: chr1-197316435;