1-197314055-C-T

Position:

• chr1-197314055-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.71-14367C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,028 control chromosomes in the GnomAD database, including 36,438 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 0.69 (36438 hom., cov: 32)
• Consequence: CRB1 NM_201253.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRB1	NM_201253.3	c.71-14367C>T		intron_variant		ENST00000367400.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRB1	ENST00000367400.8	c.71-14367C>T		intron_variant		1	NM_201253.3	P1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104851 AN: 151910 Hom.: 36404 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.690 AC: 104946 AN: 152028 Hom.: 36438 Cov.: 32 AF XY: 0.692 AC XY: 51427 AN XY: 74334

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.689

Alfa AF: 0.687 Hom.: 16382

Bravo AF: 0.695

Asia WGS AF: 0.768 AC: 2672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.98
DANN	Benign	0.62

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: rs1415214; hg19: chr1-197283185;