rs2228502

Variant names:

• chr11-68781872-A-G
• rs2228502
• NM_001876.4:c.1251T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-68781872-A-G
• chr11-68781872-A-C
• chr11-68781872-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001876.4(CPT1A):​c.1251T>C​(p.Phe417Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,613,992 control chromosomes in the GnomAD database, including 710,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64534 hom., cov: 31)
  • Exomes 𝑓: 0.94 (646337 hom.)
• Consequence: CPT1A NM_001876.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.301
• Publications: 24 publications found

Genes affected

CPT1A (HGNC:2328): (carnitine palmitoyltransferase 1A) The mitochondrial oxidation of long-chain fatty acids is initiated by the sequential action of carnitine palmitoyltransferase I (which is located in the outer membrane and is detergent-labile) and carnitine palmitoyltransferase II (which is located in the inner membrane and is detergent-stable), together with a carnitine-acylcarnitine translocase. CPT I is the key enzyme in the carnitine-dependent transport across the mitochondrial inner membrane and its deficiency results in a decreased rate of fatty acid beta-oxidation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CPT1A Gene-Disease associations (from GenCC):

• carnitine palmitoyl transferase 1A deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 11-68781872-A-G is Benign according to our data. Variant chr11-68781872-A-G is described in ClinVar as Benign. ClinVar VariationId is 166951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.301 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001876.4. 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
	CPT1A	NM_001876.4	MANE Select	c.1251T>C	p.Phe417Phe	synonymous	Exon 11 of 19	NP_001867.2	P50416-1
	CPT1A	NM_001440358.1		c.1251T>C	p.Phe417Phe	synonymous	Exon 11 of 19	NP_001427287.1
	CPT1A	NM_001440359.1		c.1251T>C	p.Phe417Phe	synonymous	Exon 12 of 20	NP_001427288.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1A	ENST00000265641.10	TSL:1 MANE Select	c.1251T>C	p.Phe417Phe	synonymous	Exon 11 of 19	ENSP00000265641.4	P50416-1
	CPT1A	ENST00000376618.6	TSL:1	c.1251T>C	p.Phe417Phe	synonymous	Exon 11 of 19	ENSP00000365803.2	P50416-2
	CPT1A	ENST00000540367.5	TSL:1	c.1251T>C	p.Phe417Phe	synonymous	Exon 10 of 18	ENSP00000439084.1	P50416-2

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139810 AN: 152042 Hom.: 64499 Cov.: 31

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.977

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.921

GnomAD2 exomes AF: 0.933 AC: 234614 AN: 251492 AF XY: 0.932

Gnomad AFR exome AF: 0.843

Gnomad AMR exome AF: 0.946

Gnomad ASJ exome AF: 0.952

Gnomad EAS exome AF: 0.909

Gnomad FIN exome AF: 0.972

Gnomad NFE exome AF: 0.949

Gnomad OTH exome AF: 0.937

GnomAD4 exome AF: 0.940 AC: 1374100 AN: 1461832 Hom.: 646337 Cov.: 51 AF XY: 0.939 AC XY: 682611 AN XY: 727228

African (AFR) AF: 0.845 AC: 28277 AN: 33480

American (AMR) AF: 0.944 AC: 42209 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 24891 AN: 26136

East Asian (EAS) AF: 0.918 AC: 36440 AN: 39700

South Asian (SAS) AF: 0.885 AC: 76357 AN: 86258

European-Finnish (FIN) AF: 0.970 AC: 51815 AN: 53418

Middle Eastern (MID) AF: 0.880 AC: 5073 AN: 5766

European-Non Finnish (NFE) AF: 0.947 AC: 1053034 AN: 1111956

Other (OTH) AF: 0.927 AC: 56004 AN: 60394

GnomAD4 genome AF: 0.919 AC: 139902 AN: 152160 Hom.: 64534 Cov.: 31 AF XY: 0.921 AC XY: 68500 AN XY: 74394

African (AFR) AF: 0.849 AC: 35218 AN: 41488

American (AMR) AF: 0.944 AC: 14419 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.949 AC: 3294 AN: 3472

East Asian (EAS) AF: 0.910 AC: 4690 AN: 5154

South Asian (SAS) AF: 0.890 AC: 4290 AN: 4822

European-Finnish (FIN) AF: 0.977 AC: 10355 AN: 10600

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.949 AC: 64549 AN: 68024

Other (OTH) AF: 0.922 AC: 1947 AN: 2112

Alfa AF: 0.929 Hom.: 57133

Bravo AF: 0.914

Asia WGS AF: 0.907 AC: 3152 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Carnitine palmitoyl transferase 1A deficiency (3)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.83
DANN	Benign	0.37
PhyloP100		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs2228502; hg19: chr11-68549340; COSMIC: COSV108103820; COSMIC: COSV108103820;