9-123356238-AGCAGAGC-A

Position:

• chr9-123356238-AGCAGAGC-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_173689.7(CRB2):​c.-14_-8del 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRB2	NM_173689.7	c.-14_-8del		5_prime_UTR_variant	1/13	ENST00000373631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRB2	ENST00000373631.8	c.-14_-8del		5_prime_UTR_variant	1/13	1	NM_173689.7	P1
CRB2	ENST00000359999.7	c.-14_-8del		5_prime_UTR_variant	1/10	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

GnomAD3 exomes AF: 0.704 AC: 54404 AN: 77330 Hom.: 18952 AF XY: 0.705 AC XY: 30392 AN XY: 43138

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 SAS exome AF: 0.702

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

Gnomad4 AFR exome AF: 0.607

Gnomad4 AMR exome AF: 0.804

Gnomad4 ASJ exome AF: 0.582

Gnomad4 EAS exome AF: 0.698

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.805

Gnomad4 NFE exome AF: 0.683

Gnomad4 OTH exome AF: 0.680

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

Gnomad4 AFR AF: 0.606

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.667

Alfa AF: 0.651 Hom.: 5952

Bravo AF: 0.673

Asia WGS AF: 0.642 AC: 2231 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Ventriculomegaly-cystic kidney disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs60364866; hg19: chr9-126118517;