NM_173689.7:c.94+166G>A

Variant names:

• chr9-123356520-G-A
• rs79988079
• NM_173689.7:c.94+166G>A

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.94+166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 151,598 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.0050 (17 hom., cov: 30)
• Consequence: CRB2 NM_173689.7 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.126
• Publications: 0 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 9-123356520-G-A is Benign according to our data. Variant chr9-123356520-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1181072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0789 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.94+166G>A		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.94+166G>A		intron	N/A	ENSP00000362734.3	Q5IJ48-1
	CRB2	ENST00000896215.1		c.94+166G>A		intron	N/A	ENSP00000566274.1
	CRB2	ENST00000359999.7	TSL:2	c.94+166G>A		intron	N/A	ENSP00000353092.3	Q5IJ48-2

Frequencies

GnomAD3 genomes AF: 0.00496 AC: 751 AN: 151480 Hom.: 17 Cov.: 30

Gnomad AFR AF: 0.000705

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000525

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.0849

Gnomad SAS AF: 0.00126

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000781

Gnomad OTH AF: 0.00767

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

GnomAD4 genome AF: 0.00497 AC: 753 AN: 151598 Hom.: 17 Cov.: 30 AF XY: 0.00581 AC XY: 430 AN XY: 74036

African (AFR) AF: 0.000702 AC: 29 AN: 41284

American (AMR) AF: 0.000524 AC: 8 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3468

East Asian (EAS) AF: 0.0855 AC: 434 AN: 5074

South Asian (SAS) AF: 0.00126 AC: 6 AN: 4776

European-Finnish (FIN) AF: 0.0187 AC: 198 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000781 AC: 53 AN: 67862

Other (OTH) AF: 0.00759 AC: 16 AN: 2108

Alfa AF: 0.00344 Hom.: 1

Bravo AF: 0.00432

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.82
CADD	Benign	3.0
DANN	Benign	0.84
PhyloP100		-0.13
PromoterAI		0.0091	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: 11

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

Other links and lift over

dbSNP: rs79988079; hg19: chr9-126118799; COSMIC: COSV63501644;