rs201870376

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001199753.2(CPT1C):c.1731+7T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00635 in 1,614,164 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 33 hom. )

Consequence

CPT1C
NM_001199753.2 splice_region, intron

Scores

Splicing: ADA: 0.00001690

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.855

Publications

0 publications found

Variant links:

Genes affected

CPT1C (HGNC:18540): (carnitine palmitoyltransferase 1C) This gene encodes a member of the carnitine/choline acetyltransferase family. The encoded protein regulates the beta-oxidation and transport of long-chain fatty acids into mitochondria, and may play a role in the regulation of feeding behavior and whole-body energy homeostasis. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

CPT1C Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 73
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
hereditary spastic paraplegia
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

CPT1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.027).

BP6

Variant 19-49710491-T-A is Benign according to our data. Variant chr19-49710491-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 476172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00429 (654/152328) while in subpopulation NFE AF = 0.00701 (477/68036). AF 95% confidence interval is 0.00649. There are 2 homozygotes in GnomAd4. There are 286 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 654 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1C	NM_001199753.2 link	c.1731+7T>A		splice_region_variant, intron_variant	Intron 15 of 19	ENST00000598293.6	NP_001186682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1C	ENST00000598293.6 link	c.1731+7T>A		splice_region_variant, intron_variant	Intron 15 of 19	2	NM_001199753.2	ENSP00000473028.1

Frequencies

GnomAD3 genomes

AF:

0.00430

AC:

654

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00701

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00367

AC:

923

AN:

251180

AF XY:

0.00364

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.00745

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00217

Gnomad NFE exome

AF:

0.00559

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00656

AC:

9595

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00644

AC XY:

4681

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

33480

American (AMR)

AF:

0.00277

AC:

124

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00830

AC:

217

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00115

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00242

AC:

129

AN:

53378

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00773

AC:

8598

AN:

1112000

Other (OTH)

AF:

0.00624

AC:

377

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

502

1005

1507

2010

2512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

334

668

1002

1336

1670

<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:

0.00429

AC:

654

AN:

152328

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

286

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

41580

American (AMR)

AF:

0.00412

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00124

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00701

AC:

477

AN:

68036

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00661

Hom.:

Bravo

AF:

0.00419

EpiCase

AF:

0.00600

EpiControl

AF:

0.00622

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CPT1C: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hereditary spastic paraplegia 73

Benign:1

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.7

(source)

DANN

Benign

0.84

PhyloP100

-0.85

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.19

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over