rs201870376

Positions:

• chr19-49710491-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-49710491-T-A is Benign according to our data. Variant chr19-49710491-T-A is described in ClinVar as [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 654 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT1C	NM_001199753.2	c.1731+7T>A		splice_region_variant, intron_variant		ENST00000598293.6	NP_001186682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT1C	ENST00000598293.6	c.1731+7T>A		splice_region_variant, intron_variant		2	NM_001199753.2	ENSP00000473028.1

Frequencies

GnomAD3 genomes AF: 0.00430 AC: 654 AN: 152210 Hom.: 2 Cov.: 32

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

GnomAD3 exomes AF: 0.00367 AC: 923 AN: 251180 Hom.: 5 AF XY: 0.00364 AC XY: 495 AN XY: 135846

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 SAS exome AF: 0.00108

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.: 33 Cov.: 31 AF XY: 0.00644 AC XY: 4681 AN XY: 727214

Gnomad4 AFR exome AF: 0.00128

Gnomad4 AMR exome AF: 0.00277

Gnomad4 ASJ exome AF: 0.00830

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00115

Gnomad4 FIN exome AF: 0.00242

Gnomad4 NFE exome AF: 0.00773

Gnomad4 OTH exome AF: 0.00624

GnomAD4 genome AF: 0.00429 AC: 654 AN: 152328 Hom.: 2 Cov.: 32 AF XY: 0.00384 AC XY: 286 AN XY: 74488

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.00701

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00661 Hom.: 2

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	CPT1C: BP4, BS2 -

Hereditary spastic paraplegia 73 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 20, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.7
DANN	Benign	0.84

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

LitVar

Other links and lift over

dbSNP: rs201870376; hg19: chr19-50213748;