chr9-123356520-G-A

Position:

• chr9-123356520-G-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.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

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 9-123356520-G-A is Benign according to our data. Variant chr9-123356520-G-A is described in ClinVar as [Likely_benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRB2	NM_173689.7	c.94+166G>A		intron_variant		ENST00000373631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRB2	ENST00000373631.8	c.94+166G>A		intron_variant		1	NM_173689.7	P1
CRB2	ENST00000359999.7	c.94+166G>A		intron_variant		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

Gnomad4 AFR AF: 0.000702

Gnomad4 AMR AF: 0.000524

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.0855

Gnomad4 SAS AF: 0.00126

Gnomad4 FIN AF: 0.0187

Gnomad4 NFE AF: 0.000781

Gnomad4 OTH AF: 0.00759

Alfa AF: 0.00344 Hom.: 1

Bravo AF: 0.00432

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 23, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

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