1-197347305-T-C

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.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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.140

Publications

20 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: 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

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=-0.87).

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRB1	NM_201253.3 link	c.849-35T>C		intron_variant	Intron 3 of 11	ENST00000367400.8	NP_957705.1	P82279-1A0A7D6VM04

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRB1	ENST00000367400.8 link	c.849-35T>C		intron_variant	Intron 3 of 11	1	NM_201253.3	ENSP00000356370.3		P82279-1

Frequencies

GnomAD3 genomes

AF:

0.827

AC:

125642

AN:

151988

Hom.:

52220

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.795

AC XY:

571843

AN XY:

719466

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

11922

23843

35765

47686

59608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20184

40368

60552

80736

100920

<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:

0.827

AC:

125753

AN:

152106

Hom.:

52274

Cov.:

AF XY:

0.830

AC XY:

61677

AN XY:

74338

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1097

2194

3292

4389

5486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<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:

0.824

Hom.:

11826

Bravo

AF:

0.829

Asia WGS

AF:

0.841

AC:

2926

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Leber congenital amaurosis 8

Benign:1

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa 12

Benign:1

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pigmented paravenous retinochoroidal atrophy

Benign:1

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

9.0

(source)

DANN

Benign

0.72

PhyloP100

0.14

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over