Variant 9-123356321-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_173689.7(CRB2):c.61C>T(p.Leu21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,546,578 control chromosomes in the GnomAD database, including 2,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 469 hom., cov: 31)

Exomes 𝑓: 0.026 ( 2327 hom. )

Consequence

CRB2
NM_173689.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.84

Variant links:

Genes affected

CRB2 (HGNC:18688): (crumbs cell polarity complex component 2) This gene encodes a member of a family of proteins that are components of the Crumbs cell polarity complex. In mammals, members of this family are thought to play a role in many cellular processes in early embryonic development. A similar protein in Drosophila determines apicobasal polarity in embryonic epithelial cells. Mutations in this gene are associated with focal segmental glomerulosclerosis 9, and with ventriculomegaly with cystic kidney disease. [provided by RefSeq, Aug 2016]

CRB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 9-123356321-C-T is Benign according to our data. Variant chr9-123356321-C-T is described in ClinVar as [Benign]. Clinvar id is 1166112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.84 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRB2	NM_173689.7 linkuse as main transcript	c.61C>T	p.Leu21=	synonymous_variant	1/13	ENST00000373631.8	NP_775960.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRB2	ENST00000373631.8 linkuse as main transcript	c.61C>T	p.Leu21=	synonymous_variant	1/13	1	NM_173689.7	ENSP00000362734	P1	Q5IJ48-1
CRB2	ENST00000359999.7 linkuse as main transcript	c.61C>T	p.Leu21=	synonymous_variant	1/10	2		ENSP00000353092		Q5IJ48-2

Frequencies

GnomAD3 genomes

AF:

0.0565

AC:

8597

AN:

152096

Hom.:

470

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0984

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0467

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.0425

GnomAD3 exomes

AF:

0.0707

AC:

10658

AN:

150648

Hom.:

859

AF XY:

0.0674

AC XY:

5385

AN XY:

79926

show subpopulations

Gnomad AFR exome

AF:

0.0938

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.146

Gnomad SAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.0487

Gnomad NFE exome

AF:

0.00786

Gnomad OTH exome

AF:

0.0509

GnomAD4 exome

AF:

0.0257

AC:

35887

AN:

1394366

Hom.:

2327

Cov.:

AF XY:

0.0276

AC XY:

18987

AN XY:

687740

show subpopulations

Gnomad4 AFR exome

AF:

0.102

Gnomad4 AMR exome

AF:

0.173

Gnomad4 ASJ exome

AF:

0.00876

Gnomad4 EAS exome

AF:

0.188

Gnomad4 SAS exome

AF:

0.111

Gnomad4 FIN exome

AF:

0.0479

Gnomad4 NFE exome

AF:

0.00591

Gnomad4 OTH exome

AF:

0.0377

GnomAD4 genome

AF:

0.0565

AC:

8607

AN:

152212

Hom.:

469

Cov.:

AF XY:

0.0614

AC XY:

4568

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0983

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.164

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.0467

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.0430

Alfa

AF:

0.0240

Hom.:

Bravo

AF:

0.0650

Asia WGS

AF:

0.175

AC:

605

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 02, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.7

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over