rs1075453

Variant names:

• chr19-49691142-G-C
• rs1075453
• NM_001199753.2:c.-282G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001199753.2(CPT1C):​c.-282G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,470 control chromosomes in the GnomAD database, including 14,311 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (14308 hom., cov: 28)
  • Exomes 𝑓: 0.27 (3 hom.)
• Consequence: CPT1C NM_001199753.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

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.-282G>C		5_prime_UTR	Exon 1 of 20	NP_001186682.1	Q8TCG5-1
	CPT1C	NM_001378482.1		c.-282G>C		5_prime_UTR	Exon 1 of 19	NP_001365411.1
	CPT1C	NM_001199752.3		c.-346G>C		5_prime_UTR	Exon 1 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.-282G>C		5_prime_UTR	Exon 1 of 20	ENSP00000473028.1	Q8TCG5-1
	CPT1C	ENST00000323446.9	TSL:1	c.-213G>C		5_prime_UTR	Exon 1 of 19	ENSP00000319343.4	Q8TCG5-1
	CPT1C	ENST00000392518.8	TSL:2	c.-346G>C		5_prime_UTR	Exon 1 of 20	ENSP00000376303.4	Q8TCG5-1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64429 AN: 151290 Hom.: 14273 Cov.: 28

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.425

GnomAD4 exome AF: 0.274 AC: 17 AN: 62 Hom.: 3 Cov.: 0 AF XY: 0.200 AC XY: 10 AN XY: 50

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.250 AC: 2 AN: 8

European-Finnish (FIN) AF: 0.333 AC: 4 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.237 AC: 9 AN: 38

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.426 AC: 64513 AN: 151408 Hom.: 14308 Cov.: 28 AF XY: 0.419 AC XY: 30982 AN XY: 74000

African (AFR) AF: 0.558 AC: 22955 AN: 41168

American (AMR) AF: 0.391 AC: 5935 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1300 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1341 AN: 5150

South Asian (SAS) AF: 0.332 AC: 1587 AN: 4786

European-Finnish (FIN) AF: 0.349 AC: 3666 AN: 10506

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26300 AN: 67832

Other (OTH) AF: 0.430 AC: 902 AN: 2100

Alfa AF: 0.405 Hom.: 1615

Bravo AF: 0.441

Asia WGS AF: 0.391 AC: 1358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		-0.26
PromoterAI		-0.041	Neutral
Mutation Taster		=300/0	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: rs1075453; hg19: chr19-50194399;