9-123356192-G-T

Position:

• chr9-123356192-G-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000359999.7(CRB2):​c.-69G>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0553 in 1,094,622 control chromosomes in the GnomAD database, including 1,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (220 hom., cov: 31)
  • Exomes 𝑓: 0.056 (1557 hom.)
• Consequence: CRB2 ENST00000359999.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.26

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 9-123356192-G-T is Benign according to our data. Variant chr9-123356192-G-T is described in ClinVar as [Benign]. Clinvar id is 1288801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRB2	NM_173689.7			upstream_gene_variant		ENST00000373631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRB2	ENST00000359999.7	c.-69G>T		5_prime_UTR_variant	1/10	2
CRB2	ENST00000373631.8			upstream_gene_variant		1	NM_173689.7	P1

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8170 AN: 151740 Hom.: 219 Cov.: 31

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0357

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.0459

Gnomad SAS AF: 0.0483

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.0513

GnomAD4 exome AF: 0.0556 AC: 52406 AN: 942764 Hom.: 1557 Cov.: 12 AF XY: 0.0550 AC XY: 25606 AN XY: 465536

Gnomad4 AFR exome AF: 0.0515

Gnomad4 AMR exome AF: 0.0245

Gnomad4 ASJ exome AF: 0.0511

Gnomad4 EAS exome AF: 0.0315

Gnomad4 SAS exome AF: 0.0396

Gnomad4 FIN exome AF: 0.0459

Gnomad4 NFE exome AF: 0.0590

Gnomad4 OTH exome AF: 0.0563

GnomAD4 genome AF: 0.0538 AC: 8176 AN: 151858 Hom.: 220 Cov.: 31 AF XY: 0.0529 AC XY: 3925 AN XY: 74232

Gnomad4 AFR AF: 0.0567

Gnomad4 AMR AF: 0.0357

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.0456

Gnomad4 SAS AF: 0.0475

Gnomad4 FIN AF: 0.0419

Gnomad4 NFE AF: 0.0586

Gnomad4 OTH AF: 0.0541

Alfa AF: 0.0327 Hom.: 27

Bravo AF: 0.0529

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.97

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35454517; hg19: chr9-126118471;