rs73750949

Variant names:

• chr5-37182838-T-A
• rs73750949
• NM_001384732.1:c.5343A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-37182838-T-A
• chr5-37182838-T-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001384732.1(CPLANE1):​c.5343A>T​(p.Thr1781Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,613,574 control chromosomes in the GnomAD database, including 374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (200 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (174 hom.)
• Consequence: CPLANE1 NM_001384732.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.00100
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 5-37182838-T-A is Benign according to our data. Variant chr5-37182838-T-A is described in ClinVar as Benign. ClinVar VariationId is 158039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.001 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0907 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.5343A>T	p.Thr1781Thr	synonymous	Exon 26 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.5343A>T	p.Thr1781Thr	synonymous	Exon 26 of 52	NP_075561.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLANE1	ENST00000651892.2	MANE Select	c.5343A>T	p.Thr1781Thr	synonymous	Exon 26 of 53	ENSP00000498265.2	A0A494BZW6
	CPLANE1	ENST00000514429.5	TSL:1	c.2487A>T	p.Thr829Thr	synonymous	Exon 11 of 37	ENSP00000424223.1	H0Y9I8
	CPLANE1	ENST00000509849.5	TSL:1	n.2358A>T		non_coding_transcript_exon	Exon 11 of 37	ENSP00000426337.1	H0YA77

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4100 AN: 152176 Hom.: 200 Cov.: 32

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0215

GnomAD2 exomes AF: 0.00716 AC: 1795 AN: 250638 AF XY: 0.00500

Gnomad AFR exome AF: 0.0996

Gnomad AMR exome AF: 0.00451

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00269 AC: 3937 AN: 1461280 Hom.: 174 Cov.: 32 AF XY: 0.00225 AC XY: 1633 AN XY: 726916

African (AFR) AF: 0.0981 AC: 3282 AN: 33452

American (AMR) AF: 0.00511 AC: 228 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.000221 AC: 19 AN: 86092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5764

European-Non Finnish (NFE) AF: 0.0000423 AC: 47 AN: 1111842

Other (OTH) AF: 0.00571 AC: 345 AN: 60374

GnomAD4 genome AF: 0.0270 AC: 4107 AN: 152294 Hom.: 200 Cov.: 32 AF XY: 0.0260 AC XY: 1933 AN XY: 74468

African (AFR) AF: 0.0931 AC: 3868 AN: 41544

American (AMR) AF: 0.0118 AC: 180 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68018

Other (OTH) AF: 0.0213 AC: 45 AN: 2112

Alfa AF: 0.00163 Hom.: 7

Bravo AF: 0.0317

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	-0.36
CADD	Benign	4.1
DANN	Benign	0.71
PhyloP100		-0.0010
Mutation Taster		=99/1	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: rs73750949; hg19: chr5-37182940;