rs2786098

Variant names:

• chr1-197356778-T-A
• rs2786098
• NM_201253.3:c.989-53T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-197356778-T-A
• chr1-197356778-T-C
• chr1-197356778-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_201253.3(CRB1):​c.989-53T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000278 in 1,584,336 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: CRB1 NM_201253.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 65 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: G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• retinitis pigmentosa 12

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• 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: G2P, Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRB1	NM_201253.3	MANE Select	c.989-53T>A		intron	N/A	NP_957705.1
	CRB1	NM_001257965.2		c.782-53T>A		intron	N/A	NP_001244894.1
	CRB1	NM_001193640.2		c.653-53T>A		intron	N/A	NP_001180569.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRB1	ENST00000367400.8	TSL:1 MANE Select	c.989-53T>A		intron	N/A	ENSP00000356370.3
	CRB1	ENST00000638467.1	TSL:1	c.989-53T>A		intron	N/A	ENSP00000491102.1
	CRB1	ENST00000367399.6	TSL:1	c.653-53T>A		intron	N/A	ENSP00000356369.2

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152060 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000411

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000182 AC: 26 AN: 1432158 Hom.: 0 AF XY: 0.0000168 AC XY: 12 AN XY: 713796

African (AFR) AF: 0.000304 AC: 10 AN: 32856

American (AMR) AF: 0.000135 AC: 6 AN: 44314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25936

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39544

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000368 AC: 4 AN: 1086090

Other (OTH) AF: 0.0000505 AC: 3 AN: 59458

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74388

African (AFR) AF: 0.000409 AC: 17 AN: 41530

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 187228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.032
DANN	Benign	0.23
PhyloP100		-2.0

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: rs2786098; hg19: chr1-197325908;