rs114126795

Variant names:

• chr5-37153827-G-A
• rs114126795
• NM_001384732.1:c.8286C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-37153827-G-A
• chr5-37153827-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001384732.1(CPLANE1):​c.8286C>T​(p.Asp2762Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00767 in 1,614,050 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0079 (85 hom.)
• Consequence: CPLANE1 NM_001384732.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.298
• Publications: 3 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, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Illumina
• orofaciodigital syndrome type 6

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-37153827-G-A is Benign according to our data. Variant chr5-37153827-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 158054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.298 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00575 (875/152240) while in subpopulation SAS AF = 0.0143 (69/4820). AF 95% confidence interval is 0.0116. There are 4 homozygotes in GnomAd4. There are 456 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384732.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	NM_001384732.1	MANE Select	c.8286C>T	p.Asp2762Asp	synonymous	Exon 42 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.8124C>T	p.Asp2708Asp	synonymous	Exon 41 of 52	NP_075561.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.8286C>T	p.Asp2762Asp	synonymous	Exon 42 of 53	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000514429.5	TSL:1	c.5322C>T	p.Asp1774Asp	synonymous	Exon 26 of 37	ENSP00000424223.1	H0Y9I8
	CPLANE1	ENST00000509849.5	TSL:1	n.5298C>T		non_coding_transcript_exon	Exon 27 of 37	ENSP00000426337.1	H0YA77

Frequencies

GnomAD3 genomes AF: 0.00576 AC: 876 AN: 152122 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00717

Gnomad OTH AF: 0.00623

GnomAD2 exomes AF: 0.00636 AC: 1598 AN: 251326 AF XY: 0.00674

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0159

Gnomad NFE exome AF: 0.00639

Gnomad OTH exome AF: 0.00570

GnomAD4 exome AF: 0.00787 AC: 11511 AN: 1461810 Hom.: 85 Cov.: 31 AF XY: 0.00787 AC XY: 5722 AN XY: 727210

African (AFR) AF: 0.00111 AC: 37 AN: 33474

American (AMR) AF: 0.00177 AC: 79 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000918 AC: 24 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0134 AC: 1155 AN: 86254

European-Finnish (FIN) AF: 0.0164 AC: 875 AN: 53406

Middle Eastern (MID) AF: 0.0108 AC: 62 AN: 5766

European-Non Finnish (NFE) AF: 0.00796 AC: 8856 AN: 1111974

Other (OTH) AF: 0.00699 AC: 422 AN: 60396

GnomAD4 genome AF: 0.00575 AC: 875 AN: 152240 Hom.: 4 Cov.: 32 AF XY: 0.00613 AC XY: 456 AN XY: 74436

African (AFR) AF: 0.00132 AC: 55 AN: 41534

American (AMR) AF: 0.00320 AC: 49 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4820

European-Finnish (FIN) AF: 0.0183 AC: 194 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00717 AC: 488 AN: 68026

Other (OTH) AF: 0.00617 AC: 13 AN: 2108

Alfa AF: 0.00413 Hom.: 2

Bravo AF: 0.00417

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.00611

EpiControl AF: 0.00593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Joubert syndrome 17 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.9
DANN	Benign	0.27
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism

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: rs114126795; hg19: chr5-37153929; COSMIC: COSV57056523; COSMIC: COSV57056523;