chr9-123362696-T-C

Variant names:

• chr9-123362696-T-C
• rs56366974
• NM_173689.7:c.95-169T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_173689.7(CRB2):​c.95-169T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,846 control chromosomes in the GnomAD database, including 8,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (8578 hom., cov: 31)
• Consequence: CRB2 NM_173689.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.74
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-123362696-T-C is Benign according to our data. Variant chr9-123362696-T-C is described in ClinVar as Benign. ClinVar VariationId is 1180383.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 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.95-169T>C		intron	N/A	NP_775960.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRB2	ENST00000373631.8	TSL:1 MANE Select	c.95-169T>C		intron	N/A	ENSP00000362734.3	Q5IJ48-1
	CRB2	ENST00000896215.1		c.95-169T>C		intron	N/A	ENSP00000566274.1
	CRB2	ENST00000359999.7	TSL:2	c.95-169T>C		intron	N/A	ENSP00000353092.3	Q5IJ48-2

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49876 AN: 151728 Hom.: 8584 Cov.: 31

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.329

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.328 AC: 49867 AN: 151846 Hom.: 8578 Cov.: 31 AF XY: 0.328 AC XY: 24327 AN XY: 74230

African (AFR) AF: 0.228 AC: 9427 AN: 41392

American (AMR) AF: 0.323 AC: 4936 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1107 AN: 3470

East Asian (EAS) AF: 0.381 AC: 1960 AN: 5146

South Asian (SAS) AF: 0.333 AC: 1598 AN: 4798

European-Finnish (FIN) AF: 0.356 AC: 3761 AN: 10554

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 25986 AN: 67888

Other (OTH) AF: 0.327 AC: 689 AN: 2110

Alfa AF: 0.336 Hom.: 2753

Bravo AF: 0.318

Asia WGS AF: 0.309 AC: 1079 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.018
DANN	Benign	0.76
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs56366974; hg19: chr9-126124975;