rs1337167

Variant names:

• chr1-197347305-T-C
• rs1337167
• NM_201253.3:c.849-35T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-197347305-T-C
• chr1-197347305-T-A
• chr1-197347305-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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 -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 VariationId 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.

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.849-35T>C		intron	N/A	NP_957705.1	P82279-1
	CRB1	NM_001257965.2		c.642-35T>C		intron	N/A	NP_001244894.1	F5H0L2
	CRB1	NM_001193640.2		c.653-9526T>C		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.849-35T>C		intron	N/A	ENSP00000356370.3	P82279-1
	CRB1	ENST00000638467.1	TSL:1	c.849-35T>C		intron	N/A	ENSP00000491102.1	P82279-2
	CRB1	ENST00000367399.6	TSL:1	c.653-9526T>C		intron	N/A	ENSP00000356369.2	P82279-3

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

GnomAD2 exomes AF: 0.816 AC: 205112 AN: 251248 AF XY: 0.818

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 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

African (AFR) AF: 0.917 AC: 30394 AN: 33128

American (AMR) AF: 0.832 AC: 37197 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 20886 AN: 26028

East Asian (EAS) AF: 0.789 AC: 31243 AN: 39602

South Asian (SAS) AF: 0.883 AC: 75747 AN: 85824

European-Finnish (FIN) AF: 0.802 AC: 42733 AN: 53294

Middle Eastern (MID) AF: 0.852 AC: 4873 AN: 5722

European-Non Finnish (NFE) AF: 0.778 AC: 852497 AN: 1095582

Other (OTH) AF: 0.811 AC: 48485 AN: 59752

GnomAD4 genome AF: 0.827 AC: 125753 AN: 152106 Hom.: 52274 Cov.: 31 AF XY: 0.830 AC XY: 61677 AN XY: 74338

African (AFR) AF: 0.907 AC: 37675 AN: 41530

American (AMR) AF: 0.825 AC: 12600 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2770 AN: 3468

East Asian (EAS) AF: 0.778 AC: 4021 AN: 5168

South Asian (SAS) AF: 0.884 AC: 4265 AN: 4824

European-Finnish (FIN) AF: 0.805 AC: 8493 AN: 10552

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53303 AN: 67982

Other (OTH) AF: 0.834 AC: 1755 AN: 2104

Alfa AF: 0.824 Hom.: 11826

Bravo AF: 0.829

Asia WGS AF: 0.841 AC: 2926 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Leber congenital amaurosis 8 (1)
-	-	1	not specified (1)
-	-	1	Pigmented paravenous retinochoroidal atrophy (1)
-	-	1	Retinitis pigmentosa 12 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.0
DANN	Benign	0.72
PhyloP100		0.14
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: rs1337167; hg19: chr1-197316435;