rs2808416

Variant names:

• chr9-123357880-A-G
• rs2808416
• NM_173689.7:c.94+1526A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: G2P, Genomics England PanelApp, Orphanet
• 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 -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 rank	MANE	Protein	UniProt
CRB2	NM_173689.7	c.94+1526A>G		intron_variant	Intron 1 of 12	ENST00000373631.8	NP_775960.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRB2	ENST00000373631.8	c.94+1526A>G		intron_variant	Intron 1 of 12	1	NM_173689.7	ENSP00000362734.3
CRB2	ENST00000359999.7	c.94+1526A>G		intron_variant	Intron 1 of 9	2		ENSP00000353092.3

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

African (AFR) AF: 0.736 AC: 30561 AN: 41550

American (AMR) AF: 0.796 AC: 12182 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2024 AN: 3468

East Asian (EAS) AF: 0.714 AC: 3689 AN: 5170

South Asian (SAS) AF: 0.704 AC: 3403 AN: 4832

European-Finnish (FIN) AF: 0.817 AC: 8676 AN: 10618

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46212 AN: 67988

Other (OTH) AF: 0.687 AC: 1450 AN: 2112

Alfa AF: 0.681 Hom.: 59328

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
PhyloP100		-0.95
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: rs2808416; hg19: chr9-126120159;