rs2808416

Positions:

• chr9-123357880-A-G
• chr9-123357880-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173689.7(CRB2):​c.94+1526A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,256 control chromosomes in the GnomAD database, including 39,259 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (39259 hom., cov: 36)
• Consequence: CRB2 NM_173689.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRB2	NM_173689.7	c.94+1526A>G		intron_variant		ENST00000373631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRB2	ENST00000373631.8	c.94+1526A>G		intron_variant		1	NM_173689.7	P1
CRB2	ENST00000359999.7	c.94+1526A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108933 AN: 152138 Hom.: 39238 Cov.: 36

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.716 AC: 109001 AN: 152256 Hom.: 39259 Cov.: 36 AF XY: 0.722 AC XY: 53726 AN XY: 74448

Gnomad4 AFR AF: 0.736

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.687

Alfa AF: 0.681 Hom.: 44529

Bravo AF: 0.714

Asia WGS AF: 0.687 AC: 2391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.41

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: rs2808416; hg19: chr9-126120159;