rs2786098

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

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.989-53T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 1,583,332 control chromosomes in the GnomAD database, including 511,639 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52906 hom., cov: 32)
  • Exomes 𝑓: 0.80 (458733 hom.)
• Consequence: CRB1 NM_201253.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• 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: 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=-0.88).
• BP6: Variant 1-197356778-T-G is Benign according to our data. Variant chr1-197356778-T-G is described in ClinVar as Benign. ClinVar VariationId is 1177043.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.989-53T>G		intron	N/A	NP_957705.1	P82279-1
	CRB1	NM_001257965.2		c.782-53T>G		intron	N/A	NP_001244894.1	F5H0L2
	CRB1	NM_001193640.2		c.653-53T>G		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.989-53T>G		intron	N/A	ENSP00000356370.3	P82279-1
	CRB1	ENST00000638467.1	TSL:1	c.989-53T>G		intron	N/A	ENSP00000491102.1	P82279-2
	CRB1	ENST00000367399.6	TSL:1	c.653-53T>G		intron	N/A	ENSP00000356369.2	P82279-3

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126445 AN: 152020 Hom.: 52853 Cov.: 32

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.836

GnomAD4 exome AF: 0.800 AC: 1144243 AN: 1431194 Hom.: 458733 AF XY: 0.801 AC XY: 571744 AN XY: 713350

African (AFR) AF: 0.918 AC: 30169 AN: 32848

American (AMR) AF: 0.834 AC: 36974 AN: 44308

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 20407 AN: 25928

East Asian (EAS) AF: 0.789 AC: 31196 AN: 39536

South Asian (SAS) AF: 0.884 AC: 75307 AN: 85158

European-Finnish (FIN) AF: 0.814 AC: 43203 AN: 53052

Middle Eastern (MID) AF: 0.854 AC: 4875 AN: 5710

European-Non Finnish (NFE) AF: 0.787 AC: 853597 AN: 1085242

Other (OTH) AF: 0.817 AC: 48515 AN: 59412

GnomAD4 genome AF: 0.832 AC: 126555 AN: 152138 Hom.: 52906 Cov.: 32 AF XY: 0.835 AC XY: 62098 AN XY: 74366

African (AFR) AF: 0.908 AC: 37702 AN: 41520

American (AMR) AF: 0.830 AC: 12685 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2720 AN: 3470

East Asian (EAS) AF: 0.779 AC: 4025 AN: 5164

South Asian (SAS) AF: 0.887 AC: 4275 AN: 4820

European-Finnish (FIN) AF: 0.817 AC: 8646 AN: 10586

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

European-Non Finnish (NFE) AF: 0.792 AC: 53862 AN: 67984

Other (OTH) AF: 0.838 AC: 1767 AN: 2108

Alfa AF: 0.804 Hom.: 187228

Bravo AF: 0.833

Asia WGS AF: 0.842 AC: 2929 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	Pigmented paravenous retinochoroidal atrophy (1)
-	-	1	Retinitis pigmentosa 12 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.036
DANN	Benign	0.53
PhyloP100		-2.0
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: rs2786098; hg19: chr1-197325908;