9-123356192-G-T

Variant names:

• chr9-123356192-G-T
• rs35454517
• ENST00000359999.7:c.-69G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: Genomics England PanelApp, Orphanet, 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359999.7. 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.-69G>T		upstream_gene	N/A	NP_775960.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRB2	ENST00000359999.7	TSL:2	c.-69G>T		5_prime_UTR	Exon 1 of 10	ENSP00000353092.3	Q5IJ48-2
	CRB2	ENST00000373631.8	TSL:1 MANE Select	c.-69G>T		upstream_gene	N/A	ENSP00000362734.3	Q5IJ48-1
	CRB2	ENST00000896215.1		c.-69G>T		upstream_gene	N/A	ENSP00000566274.1

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

African (AFR) AF: 0.0515 AC: 1035 AN: 20104

American (AMR) AF: 0.0245 AC: 436 AN: 17792

Ashkenazi Jewish (ASJ) AF: 0.0511 AC: 835 AN: 16342

East Asian (EAS) AF: 0.0315 AC: 944 AN: 30008

South Asian (SAS) AF: 0.0396 AC: 1979 AN: 50018

European-Finnish (FIN) AF: 0.0459 AC: 1372 AN: 29900

Middle Eastern (MID) AF: 0.0542 AC: 161 AN: 2972

European-Non Finnish (NFE) AF: 0.0590 AC: 43319 AN: 734304

Other (OTH) AF: 0.0563 AC: 2325 AN: 41324

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

African (AFR) AF: 0.0567 AC: 2347 AN: 41392

American (AMR) AF: 0.0357 AC: 545 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3472

East Asian (EAS) AF: 0.0456 AC: 234 AN: 5132

South Asian (SAS) AF: 0.0475 AC: 228 AN: 4804

European-Finnish (FIN) AF: 0.0419 AC: 444 AN: 10594

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0586 AC: 3976 AN: 67872

Other (OTH) AF: 0.0541 AC: 114 AN: 2106

Alfa AF: 0.0331 Hom.: 29

Bravo AF: 0.0529

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.97
PhyloP100		5.3
PromoterAI		-0.17	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs35454517; hg19: chr9-126118471;