NM_201253.3:c.71-14367C>T

Variant names:

• chr1-197314055-C-T
• rs1415214
• NM_201253.3:c.71-14367C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• hereditary macular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Leber congenital amaurosis 8

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P
• retinitis pigmentosa 12

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• nanophthalmia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pigmented paravenous retinochoroidal atrophy

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201253.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRB1	NM_201253.3	MANE Select	c.71-14367C>T		intron	N/A	NP_957705.1	P82279-1
	CRB1	NM_001257965.2		c.-138+9642C>T		intron	N/A	NP_001244894.1	F5H0L2
	CRB1	NM_001193640.2		c.71-14367C>T		intron	N/A	NP_001180569.1	P82279-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRB1	ENST00000367400.8	TSL:1 MANE Select	c.71-14367C>T		intron	N/A	ENSP00000356370.3	P82279-1
	CRB1	ENST00000638467.1	TSL:1	c.71-14367C>T		intron	N/A	ENSP00000491102.1	P82279-2
	CRB1	ENST00000367399.6	TSL:1	c.71-14367C>T		intron	N/A	ENSP00000356369.2	P82279-3

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

African (AFR) AF: 0.663 AC: 27483 AN: 41452

American (AMR) AF: 0.735 AC: 11223 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2292 AN: 3468

East Asian (EAS) AF: 0.918 AC: 4750 AN: 5176

South Asian (SAS) AF: 0.700 AC: 3373 AN: 4820

European-Finnish (FIN) AF: 0.682 AC: 7203 AN: 10568

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46335 AN: 67954

Other (OTH) AF: 0.689 AC: 1452 AN: 2106

Alfa AF: 0.687 Hom.: 18215

Bravo AF: 0.695

Asia WGS AF: 0.768 AC: 2672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.98
DANN	Benign	0.62
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1415214; hg19: chr1-197283185;