chr5-37081603-A-G

Variant names:

• chr5-37081603-A-G
• rs300046
• XM_047417561.1:c.9580-1782T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047417561.1(CPLANE1):​c.9580-1782T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,734 control chromosomes in the GnomAD database, including 29,489 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 0.60 (29489 hom., cov: 29)
• Consequence: CPLANE1 XM_047417561.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 9 publications found

Genes affected

CPLANE1 (HGNC:25801): (ciliogenesis and planar polarity effector complex subunit 1) The protein encoded by this gene has putative coiled-coil domains and may be a transmembrane protein. Defects in this gene are a cause of Joubert syndrome (JBTS). [provided by RefSeq, May 2012]

CPLANE1 Gene-Disease associations (from GenCC):

• Joubert syndrome 17

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, ClinGen, G2P, Illumina, Labcorp Genetics (formerly Invitae)
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90558 AN: 151614 Hom.: 29432 Cov.: 29

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.598 AC: 90678 AN: 151734 Hom.: 29489 Cov.: 29 AF XY: 0.598 AC XY: 44306 AN XY: 74140

African (AFR) AF: 0.871 AC: 36064 AN: 41422

American (AMR) AF: 0.612 AC: 9330 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1906 AN: 3470

East Asian (EAS) AF: 0.510 AC: 2591 AN: 5082

South Asian (SAS) AF: 0.569 AC: 2727 AN: 4792

European-Finnish (FIN) AF: 0.431 AC: 4529 AN: 10508

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31720 AN: 67902

Other (OTH) AF: 0.601 AC: 1265 AN: 2106

Alfa AF: 0.547 Hom.: 3019

Bravo AF: 0.623

Asia WGS AF: 0.567 AC: 1973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.60
PhyloP100		-0.50

Splicing

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

Other links and lift over

dbSNP: rs300046; hg19: chr5-37081705;