dbSNP rs74478954: CPLANE1:p.Val1265Val (chr5-37195874-A-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001384732.1(CPLANE1):c.3795T>A(p.Val1265Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00564 in 1,610,988 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 49 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 67 hom. )

Consequence

CPLANE1
NM_001384732.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.01

Publications

4 publications found

Variant links:

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

CPLANE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 5-37195874-A-T is Benign according to our data. Variant chr5-37195874-A-T is described in ClinVar as Benign. ClinVar VariationId is 158033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0155 (2366/152236) while in subpopulation AFR AF = 0.0469 (1948/41530). AF 95% confidence interval is 0.0452. There are 49 homozygotes in GnomAd4. There are 1135 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 49 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.3795T>A	p.Val1265Val	synonymous	Exon 21 of 53	NP_001371661.1	A0A494BZW6
	CPLANE1	NM_023073.4		c.3795T>A	p.Val1265Val	synonymous	Exon 21 of 52	NP_075561.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CPLANE1	ENST00000651892.2	MANE Select	c.3795T>A	p.Val1265Val	synonymous	Exon 21 of 53	ENSP00000498265.2	A0A494BZW6
CPLANE1	ENST00000514429.5	TSL:1	c.939T>A	p.Val313Val	synonymous	Exon 6 of 37	ENSP00000424223.1	H0Y9I8
CPLANE1	ENST00000509849.5	TSL:1	n.810T>A		non_coding_transcript_exon	Exon 6 of 37	ENSP00000426337.1	H0YA77

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2362

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00331

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.00685

AC:

1700

AN:

248134

AF XY:

0.00663

show subpopulations

Gnomad AFR exome

AF:

0.0485

Gnomad AMR exome

AF:

0.00504

Gnomad ASJ exome

AF:

0.000501

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000926

Gnomad NFE exome

AF:

0.00393

Gnomad OTH exome

AF:

0.00548

GnomAD4 exome

AF:

0.00461

AC:

6720

AN:

1458752

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

3495

AN XY:

725652

show subpopulations

African (AFR)

AF:

0.0502

AC:

1671

AN:

33276

American (AMR)

AF:

0.00542

AC:

239

AN:

44058

Ashkenazi Jewish (ASJ)

AF:

0.000423

AC:

AN:

26030

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39528

South Asian (SAS)

AF:

0.0101

AC:

867

AN:

85500

European-Finnish (FIN)

AF:

0.000131

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.0217

AC:

125

AN:

5748

European-Non Finnish (NFE)

AF:

0.00306

AC:

3399

AN:

1111032

Other (OTH)

AF:

0.00664

AC:

400

AN:

60218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

309

617

926

1234

1543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0155

AC:

2366

AN:

152236

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1135

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0469

AC:

1948

AN:

41530

American (AMR)

AF:

0.00693

AC:

106

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00995

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00331

AC:

225

AN:

68012

Other (OTH)

AF:

0.0132

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

116

232

347

463

579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00646

Hom.:

Bravo

AF:

0.0177

Asia WGS

AF:

0.00289

AC:

AN:

3476

EpiCase

AF:

0.00369

EpiControl

AF:

0.00645

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Joubert syndrome 17 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.2

(source)

DANN

Benign

0.80

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.25

Position offset: 3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over