1-197356778-T-G

Position:

• chr1-197356778-T-G

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.989-53T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 1,583,332 control chromosomes in the GnomAD database, including 511,639 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52906 hom., cov: 32)
  • Exomes 𝑓: 0.80 (458733 hom.)
• Consequence: CRB1 NM_201253.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.96

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=-0.88).
• BP6: Variant 1-197356778-T-G is Benign according to our data. Variant chr1-197356778-T-G is described in ClinVar as [Benign]. Clinvar id is 1177043.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.989-53T>G		intron_variant		ENST00000367400.8	NP_957705.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRB1	ENST00000367400.8	c.989-53T>G		intron_variant		1	NM_201253.3	ENSP00000356370.3

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126445 AN: 152020 Hom.: 52853 Cov.: 32

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.836

GnomAD4 exome AF: 0.800 AC: 1144243 AN: 1431194 Hom.: 458733 AF XY: 0.801 AC XY: 571744 AN XY: 713350

Gnomad4 AFR exome AF: 0.918

Gnomad4 AMR exome AF: 0.834

Gnomad4 ASJ exome AF: 0.787

Gnomad4 EAS exome AF: 0.789

Gnomad4 SAS exome AF: 0.884

Gnomad4 FIN exome AF: 0.814

Gnomad4 NFE exome AF: 0.787

Gnomad4 OTH exome AF: 0.817

GnomAD4 genome AF: 0.832 AC: 126555 AN: 152138 Hom.: 52906 Cov.: 32 AF XY: 0.835 AC XY: 62098 AN XY: 74366

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.887

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.792

Gnomad4 OTH AF: 0.838

Alfa AF: 0.796 Hom.: 79987

Bravo AF: 0.833

Asia WGS AF: 0.842 AC: 2929 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

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	- -

Leber congenital amaurosis 8 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Retinitis pigmentosa 12 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Pigmented paravenous retinochoroidal atrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.036
DANN	Benign	0.53

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: rs2786098; hg19: chr1-197325908;