22-50571058-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_152246.3(CPT1B):c.1876-15A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,613,344 control chromosomes in the GnomAD database, including 252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0095 ( 12 hom., cov: 33)

Exomes 𝑓: 0.015 ( 240 hom. )

Consequence

CPT1B
NM_152246.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign/Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: -2.44

Variant links:

Genes affected

CPT1B (HGNC:2329): (carnitine palmitoyltransferase 1B) The protein encoded by this gene, a member of the carnitine/choline acetyltransferase family, is the rate-controlling enzyme of the long-chain fatty acid beta-oxidation pathway in muscle mitochondria. This enzyme is required for the net transport of long-chain fatty acyl-CoAs from the cytoplasm into the mitochondria. Multiple transcript variants encoding different isoforms have been found for this gene, and read-through transcripts are expressed from the upstream locus that include exons from this gene. [provided by RefSeq, Jun 2009]

CPT1B links:

CHKB-CPT1B (HGNC:):

CHKB-CPT1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 22-50571058-T-C is Benign according to our data. Variant chr22-50571058-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1285039.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-50571058-T-C is described in Lovd as [Likely_benign]. Variant chr22-50571058-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00949 (1444/152186) while in subpopulation NFE AF= 0.017 (1157/67992). AF 95% confidence interval is 0.0162. There are 12 homozygotes in gnomad4. There are 684 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPT1B	NM_152246.3 linkuse as main transcript	c.1876-15A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000312108.12
CHKB-CPT1B	NR_027928.2 linkuse as main transcript	n.3441-15A>G		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPT1B	ENST00000312108.12 linkuse as main transcript	c.1876-15A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_152246.3	P1	Q92523-1

Frequencies

GnomAD3 genomes

AF:

0.00950

AC:

1444

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00934

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0170

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00990

AC:

2464

AN:

248888

Hom.:

AF XY:

0.0101

AC XY:

1359

AN XY:

134740

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.00398

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.0106

Gnomad NFE exome

AF:

0.0177

Gnomad OTH exome

AF:

0.00867

GnomAD4 exome

AF:

0.0151

AC:

22011

AN:

1461158

Hom.:

240

Cov.:

AF XY:

0.0148

AC XY:

10754

AN XY:

726762

show subpopulations

Gnomad4 AFR exome

AF:

0.00281

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.00356

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000846

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.0183

Gnomad4 OTH exome

AF:

0.0114

GnomAD4 genome

AF:

0.00949

AC:

1444

AN:

152186

Hom.:

Cov.:

AF XY:

0.00919

AC XY:

684

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00934

Gnomad4 NFE

AF:

0.0170

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.0116

Hom.:

Bravo

AF:

0.00890

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

Cadd

Benign

0.0090

Dann

Benign

0.48

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over