rs41302107

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_201253.3(CRB1):c.*28T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 1,600,232 control chromosomes in the GnomAD database, including 6,713 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 467 hom., cov: 32)

Exomes 𝑓: 0.087 ( 6246 hom. )

Consequence

CRB1
NM_201253.3 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.751

Publications

11 publications found

Variant links:

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

CRB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-197477907-T-C is Benign according to our data. Variant chr1-197477907-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 263259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.094 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CRB1	NM_201253.3	MANE Select	c.*28T>C	3_prime_UTR	Exon 12 of 12	NP_957705.1	P82279-1
CRB1	NM_001257965.2		c.*28T>C	3_prime_UTR	Exon 15 of 15	NP_001244894.1	F5H0L2
CRB1	NM_001193640.2		c.*28T>C	3_prime_UTR	Exon 10 of 10	NP_001180569.1	P82279-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CRB1	ENST00000367400.8	TSL:1 MANE Select	c.*28T>C	3_prime_UTR	Exon 12 of 12	ENSP00000356370.3	P82279-1
CRB1	ENST00000448952.1	TSL:1	c.*354T>C	3_prime_UTR	Exon 2 of 2	ENSP00000395407.1	A0A0C4DG35
CRB1	ENST00000484075.5	TSL:1	n.*360T>C	non_coding_transcript_exon	Exon 12 of 12	ENSP00000433932.1	P82279-2

Frequencies

GnomAD3 genomes

AF:

0.0680

AC:

10337

AN:

152052

Hom.:

467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0402

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.0566

Gnomad ASJ

AF:

0.0438

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0187

Gnomad FIN

AF:

0.0649

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0960

Gnomad OTH

AF:

0.0622

GnomAD2 exomes

AF:

0.0615

AC:

15346

AN:

249706

AF XY:

0.0611

show subpopulations

Gnomad AFR exome

AF:

0.0376

Gnomad AMR exome

AF:

0.0399

Gnomad ASJ exome

AF:

0.0425

Gnomad EAS exome

AF:

0.00103

Gnomad FIN exome

AF:

0.0609

Gnomad NFE exome

AF:

0.0949

Gnomad OTH exome

AF:

0.0631

GnomAD4 exome

AF:

0.0866

AC:

125419

AN:

1448062

Hom.:

6246

Cov.:

AF XY:

0.0835

AC XY:

60209

AN XY:

721216

show subpopulations

African (AFR)

AF:

0.0382

AC:

1268

AN:

33180

American (AMR)

AF:

0.0430

AC:

1922

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.0446

AC:

1160

AN:

26024

East Asian (EAS)

AF:

0.000404

AC:

AN:

39614

South Asian (SAS)

AF:

0.0193

AC:

1654

AN:

85920

European-Finnish (FIN)

AF:

0.0626

AC:

3337

AN:

53348

Middle Eastern (MID)

AF:

0.0305

AC:

175

AN:

5734

European-Non Finnish (NFE)

AF:

0.102

AC:

111667

AN:

1099718

Other (OTH)

AF:

0.0705

AC:

4220

AN:

59860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

5665

11331

16996

22662

28327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4004

8008

12012

16016

20020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0679

AC:

10336

AN:

152170

Hom.:

467

Cov.:

AF XY:

0.0653

AC XY:

4858

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0401

AC:

1665

AN:

41540

American (AMR)

AF:

0.0566

AC:

864

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0438

AC:

152

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5168

South Asian (SAS)

AF:

0.0192

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.0649

AC:

688

AN:

10606

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0959

AC:

6523

AN:

67990

Other (OTH)

AF:

0.0616

AC:

130

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

486

972

1459

1945

2431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0782

Hom.:

138

Bravo

AF:

0.0675

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Leber congenital amaurosis 8 (2)

not provided (2)

Pigmented paravenous retinochoroidal atrophy (2)

not specified (1)

Retinitis pigmentosa (1)

Retinitis pigmentosa 12 (1)

Retinitis pigmentosa 12;C3151202:Leber congenital amaurosis 8 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.59

(source)

DANN

Benign

0.58

PhyloP100

-0.75

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over