rs60364866

Variant names:

• chr9-123356238-AGCAGAGC-A
• rs60364866
• NM_173689.7:c.-14_-8delCAGAGCG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_173689.7(CRB2):​c.-14_-8delCAGAGCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 1,451,146 control chromosomes in the GnomAD database, including 341,394 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (34851 hom., cov: 0)
  • Exomes 𝑓: 0.69 (306543 hom.)
• Consequence: CRB2 NM_173689.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.98
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• ventriculomegaly-cystic kidney disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, G2P
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 9-123356238-AGCAGAGC-A is Benign according to our data. Variant chr9-123356238-AGCAGAGC-A is described in ClinVar as Benign. ClinVar VariationId is 1230990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173689.7. 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
	CRB2	NM_173689.7	MANE Select	c.-14_-8delCAGAGCG		5_prime_UTR	Exon 1 of 13	NP_775960.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRB2	ENST00000373631.8	TSL:1 MANE Select	c.-14_-8delCAGAGCG		5_prime_UTR	Exon 1 of 13	ENSP00000362734.3	Q5IJ48-1
	CRB2	ENST00000896215.1		c.-14_-8delCAGAGCG		5_prime_UTR	Exon 1 of 13	ENSP00000566274.1
	CRB2	ENST00000359999.7	TSL:2	c.-14_-8delCAGAGCG		5_prime_UTR	Exon 1 of 10	ENSP00000353092.3	Q5IJ48-2

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102088 AN: 150922 Hom.: 34839 Cov.: 0

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.670

GnomAD2 exomes AF: 0.704 AC: 54404 AN: 77330 AF XY: 0.705

Gnomad AFR exome AF: 0.604

Gnomad AMR exome AF: 0.795

Gnomad ASJ exome AF: 0.607

Gnomad EAS exome AF: 0.666

Gnomad FIN exome AF: 0.820

Gnomad NFE exome AF: 0.689

Gnomad OTH exome AF: 0.701

GnomAD4 exome AF: 0.686 AC: 892061 AN: 1300104 Hom.: 306543 AF XY: 0.686 AC XY: 437549 AN XY: 637372

African (AFR) AF: 0.607 AC: 16640 AN: 27408

American (AMR) AF: 0.804 AC: 17048 AN: 21200

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 12279 AN: 21086

East Asian (EAS) AF: 0.698 AC: 22994 AN: 32960

South Asian (SAS) AF: 0.696 AC: 46982 AN: 67548

European-Finnish (FIN) AF: 0.805 AC: 29141 AN: 36192

Middle Eastern (MID) AF: 0.654 AC: 2962 AN: 4532

European-Non Finnish (NFE) AF: 0.683 AC: 707613 AN: 1035662

Other (OTH) AF: 0.680 AC: 36402 AN: 53516

GnomAD4 genome AF: 0.676 AC: 102131 AN: 151042 Hom.: 34851 Cov.: 0 AF XY: 0.682 AC XY: 50317 AN XY: 73772

African (AFR) AF: 0.606 AC: 24960 AN: 41204

American (AMR) AF: 0.785 AC: 11934 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1990 AN: 3464

East Asian (EAS) AF: 0.672 AC: 3387 AN: 5040

South Asian (SAS) AF: 0.677 AC: 3242 AN: 4790

European-Finnish (FIN) AF: 0.815 AC: 8562 AN: 10504

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 45884 AN: 67556

Other (OTH) AF: 0.667 AC: 1404 AN: 2106

Alfa AF: 0.651 Hom.: 5952

Bravo AF: 0.673

Asia WGS AF: 0.642 AC: 2231 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Ventriculomegaly-cystic kidney disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=294/6	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs60364866; hg19: chr9-126118517; COSMIC: COSV63502217; COSMIC: COSV63502217;