rs144722270

Variant names:

• chr19-49707575-C-T
• rs144722270
• NM_001199753.2:c.1401C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001199753.2(CPT1C):​c.1401C>T​(p.Ser467Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 1,613,920 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0026 (8 hom.)
• Consequence: CPT1C NM_001199753.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.64
• Publications: 0 publications found

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, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary spastic paraplegia

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP6: Variant 19-49707575-C-T is Benign according to our data. Variant chr19-49707575-C-T is described in ClinVar as Benign. ClinVar VariationId is 476169.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 = 0.0017 (259/152292) while in subpopulation NFE AF = 0.00229 (156/68028). AF 95% confidence interval is 0.002. There are 0 homozygotes in GnomAd4. There are 121 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 259 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199753.2. 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
	CPT1C	NM_001199753.2	MANE Select	c.1401C>T	p.Ser467Ser	synonymous	Exon 13 of 20	NP_001186682.1	Q8TCG5-1
	CPT1C	NM_001378482.1		c.1467C>T	p.Ser489Ser	synonymous	Exon 12 of 19	NP_001365411.1
	CPT1C	NM_001199752.3		c.1401C>T	p.Ser467Ser	synonymous	Exon 13 of 20	NP_001186681.1	Q8TCG5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1C	ENST00000598293.6	TSL:2 MANE Select	c.1401C>T	p.Ser467Ser	synonymous	Exon 13 of 20	ENSP00000473028.1	Q8TCG5-1
	CPT1C	ENST00000323446.9	TSL:1	c.1401C>T	p.Ser467Ser	synonymous	Exon 12 of 19	ENSP00000319343.4	Q8TCG5-1
	CPT1C	ENST00000405931.6	TSL:1	c.1368C>T	p.Ser456Ser	synonymous	Exon 13 of 20	ENSP00000384465.2	Q8TCG5-2

Frequencies

GnomAD3 genomes AF: 0.00170 AC: 259 AN: 152174 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00229

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00189 AC: 474 AN: 251086 AF XY: 0.00183

Gnomad AFR exome AF: 0.000862

Gnomad AMR exome AF: 0.000841

Gnomad ASJ exome AF: 0.00954

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00148

Gnomad NFE exome AF: 0.00253

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00264 AC: 3865 AN: 1461628 Hom.: 8 Cov.: 30 AF XY: 0.00254 AC XY: 1850 AN XY: 727102

African (AFR) AF: 0.000329 AC: 11 AN: 33474

American (AMR) AF: 0.00116 AC: 52 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 263 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86218

European-Finnish (FIN) AF: 0.00140 AC: 75 AN: 53406

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.00295 AC: 3280 AN: 1111888

Other (OTH) AF: 0.00286 AC: 173 AN: 60386

GnomAD4 genome AF: 0.00170 AC: 259 AN: 152292 Hom.: 0 Cov.: 31 AF XY: 0.00162 AC XY: 121 AN XY: 74472

African (AFR) AF: 0.000746 AC: 31 AN: 41554

American (AMR) AF: 0.00144 AC: 22 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000848 AC: 9 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00229 AC: 156 AN: 68028

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00282 Hom.: 0

Bravo AF: 0.00186

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00305

EpiControl AF: 0.00219

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary spastic paraplegia 73 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	4.3
DANN	Benign	0.69
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.34		Position offset: 48

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

Other links and lift over

dbSNP: rs144722270; hg19: chr19-50210832; COSMIC: COSV54917755; COSMIC: COSV54917755;