chr9-123362696-T-C

Position:

• chr9-123362696-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRB2	NM_173689.7	c.95-169T>C		intron_variant		ENST00000373631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRB2	ENST00000373631.8	c.95-169T>C		intron_variant		1	NM_173689.7	P1
CRB2	ENST00000359999.7	c.95-169T>C		intron_variant		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

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.327

Alfa AF: 0.323 Hom.: 1203

Bravo AF: 0.318

Asia WGS AF: 0.309 AC: 1079 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.018
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs56366974; hg19: chr9-126124975;