rs28514632

Variant names:

• chr5-37205364-G-A
• rs28514632
• NM_001384732.1:c.3240C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-37205364-G-A
• chr5-37205364-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001384732.1(CPLANE1):​c.3240C>T​(p.Ala1080Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,550,770 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (52 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (71 hom.)
• Consequence: CPLANE1 NM_001384732.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.34
• 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=-0.61).
• BP6: Variant 5-37205364-G-A is Benign according to our data. Variant chr5-37205364-G-A is described in ClinVar as Benign. ClinVar VariationId is 158030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.34 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0532 is higher than 0.05.

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.3240C>T	p.Ala1080Ala	synonymous	Exon 18 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.3240C>T	p.Ala1080Ala	synonymous	Exon 18 of 52	NP_075561.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.3240C>T	p.Ala1080Ala	synonymous	Exon 18 of 53	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000514429.5	TSL:1	c.384C>T	p.Ala128Ala	synonymous	Exon 3 of 37	ENSP00000424223.1	H0Y9I8
	CPLANE1	ENST00000509849.5	TSL:1	n.255C>T		non_coding_transcript_exon	Exon 3 of 37	ENSP00000426337.1	H0YA77

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2093 AN: 151952 Hom.: 50 Cov.: 33

Gnomad AFR AF: 0.0475

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00531

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00909

GnomAD2 exomes AF: 0.00312 AC: 488 AN: 156246 AF XY: 0.00241

Gnomad AFR exome AF: 0.0499

Gnomad AMR exome AF: 0.00265

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000265

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.00163 AC: 2282 AN: 1398700 Hom.: 71 Cov.: 30 AF XY: 0.00146 AC XY: 1004 AN XY: 689878

African (AFR) AF: 0.0553 AC: 1745 AN: 31540

American (AMR) AF: 0.00278 AC: 99 AN: 35644

Ashkenazi Jewish (ASJ) AF: 0.000278 AC: 7 AN: 25168

East Asian (EAS) AF: 0.00 AC: 0 AN: 35696

South Asian (SAS) AF: 0.000253 AC: 20 AN: 79120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49264

Middle Eastern (MID) AF: 0.00404 AC: 23 AN: 5696

European-Non Finnish (NFE) AF: 0.000156 AC: 168 AN: 1078606

Other (OTH) AF: 0.00380 AC: 220 AN: 57966

GnomAD4 genome AF: 0.0139 AC: 2111 AN: 152070 Hom.: 52 Cov.: 33 AF XY: 0.0140 AC XY: 1044 AN XY: 74348

African (AFR) AF: 0.0478 AC: 1980 AN: 41466

American (AMR) AF: 0.00531 AC: 81 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68000

Other (OTH) AF: 0.00900 AC: 19 AN: 2112

Alfa AF: 0.00666 Hom.: 8

Bravo AF: 0.0159

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Joubert syndrome 17 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.9
DANN	Benign	0.58
PhyloP100		1.3
Mutation Taster		=299/1	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: rs28514632; hg19: chr5-37205466;