rs61747405

Variant names:

• chr19-49708767-C-T
• rs61747405
• NM_001199753.2:c.1494C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001199753.2(CPT1C):​c.1494C>T​(p.Asp498Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 1,613,680 control chromosomes in the GnomAD database, including 598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (49 hom., cov: 30)
  • Exomes 𝑓: 0.024 (549 hom.)
• Consequence: CPT1C NM_001199753.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.18
• Publications: 3 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, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hereditary spastic paraplegia

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 19-49708767-C-T is Benign according to our data. Variant chr19-49708767-C-T is described in ClinVar as Benign. ClinVar VariationId is 476170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.18 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0241 (3671/152182) while in subpopulation NFE AF = 0.0268 (1822/67994). AF 95% confidence interval is 0.0258. There are 49 homozygotes in GnomAd4. There are 1858 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3671 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1C	NM_001199753.2	MANE Select	c.1494C>T	p.Asp498Asp	synonymous	Exon 14 of 20	NP_001186682.1
	CPT1C	NM_001378482.1		c.1560C>T	p.Asp520Asp	synonymous	Exon 13 of 19	NP_001365411.1
	CPT1C	NM_001199752.3		c.1494C>T	p.Asp498Asp	synonymous	Exon 14 of 20	NP_001186681.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1C	ENST00000598293.6	TSL:2 MANE Select	c.1494C>T	p.Asp498Asp	synonymous	Exon 14 of 20	ENSP00000473028.1
	CPT1C	ENST00000323446.9	TSL:1	c.1494C>T	p.Asp498Asp	synonymous	Exon 13 of 19	ENSP00000319343.4
	CPT1C	ENST00000405931.6	TSL:1	c.1461C>T	p.Asp487Asp	synonymous	Exon 14 of 20	ENSP00000384465.2

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3660 AN: 152064 Hom.: 49 Cov.: 30

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.00971

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0642

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.0219 AC: 5505 AN: 251392 AF XY: 0.0217

Gnomad AFR exome AF: 0.0217

Gnomad AMR exome AF: 0.00584

Gnomad ASJ exome AF: 0.0239

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.0630

Gnomad NFE exome AF: 0.0268

Gnomad OTH exome AF: 0.0218

GnomAD4 exome AF: 0.0245 AC: 35805 AN: 1461498 Hom.: 549 Cov.: 31 AF XY: 0.0240 AC XY: 17472 AN XY: 727092

African (AFR) AF: 0.0202 AC: 676 AN: 33474

American (AMR) AF: 0.00631 AC: 282 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0241 AC: 630 AN: 26132

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39700

South Asian (SAS) AF: 0.00521 AC: 449 AN: 86258

European-Finnish (FIN) AF: 0.0611 AC: 3262 AN: 53382

Middle Eastern (MID) AF: 0.00485 AC: 28 AN: 5768

European-Non Finnish (NFE) AF: 0.0261 AC: 29070 AN: 1111678

Other (OTH) AF: 0.0231 AC: 1397 AN: 60388

GnomAD4 genome AF: 0.0241 AC: 3671 AN: 152182 Hom.: 49 Cov.: 30 AF XY: 0.0250 AC XY: 1858 AN XY: 74400

African (AFR) AF: 0.0202 AC: 838 AN: 41516

American (AMR) AF: 0.00969 AC: 148 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.00560 AC: 27 AN: 4822

European-Finnish (FIN) AF: 0.0642 AC: 681 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0268 AC: 1822 AN: 67994

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.0254 Hom.: 87

Bravo AF: 0.0199

Asia WGS AF: 0.0140 AC: 48 AN: 3478

EpiCase AF: 0.0235

EpiControl AF: 0.0223

ClinVar

ClinVar submissions as Germline

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	-0.51
CADD	Benign	2.3
DANN	Benign	0.50
PhyloP100		-4.2
Mutation Taster		=100/0	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: rs61747405; hg19: chr19-50212024; COSMIC: COSV54918739; COSMIC: COSV54918739;