rs949571

chr1-197344059-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201253.3(CRB1):c.653-222C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,190 control chromosomes in the GnomAD database, including 27,512 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (27512 hom., cov: 33)
• Consequence: CRB1 NM_201253.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRB1	NM_201253.3	c.653-222C>T		intron_variant		ENST00000367400.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRB1	ENST00000367400.8	c.653-222C>T		intron_variant		1	NM_201253.3	P1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84972 AN: 152072 Hom.: 27514 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.615

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.558 AC: 84988 AN: 152190 Hom.: 27512 Cov.: 33 AF XY: 0.570 AC XY: 42397 AN XY: 74394

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.614

Alfa AF: 0.671 Hom.: 70249

Bravo AF: 0.535

Asia WGS AF: 0.731 AC: 2540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	20
Dann	Benign	0.49

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: rs949571; hg19: chr1-197313189; COSMIC: COSV66338095;