rs115830405

Variant names:

• chr22-50572314-G-A
• rs115830405
• NM_152246.3:c.1353-6C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152246.3(CPT1B):​c.1353-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,602,086 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (86 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (99 hom.)
• Consequence: CPT1B NM_152246.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002902
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

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]

CHKB-CPT1B (HGNC:41998): (CHKB-CPT1B readthrough (NMD candidate)) The genes CHKB and CPT1B are adjacent on chromosome 22 and read-through transcripts are expressed that include exons from both loci. The read-through transcripts are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to express proteins. [provided by RefSeq, Jun 2009]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 22-50572314-G-A is Benign according to our data. Variant chr22-50572314-G-A is described in ClinVar as Benign. ClinVar VariationId is 791376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1B	NM_152246.3	c.1353-6C>T		splice_region_variant, intron_variant	Intron 11 of 19	ENST00000312108.12	NP_689452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1B	ENST00000312108.12	c.1353-6C>T		splice_region_variant, intron_variant	Intron 11 of 19	1	NM_152246.3	ENSP00000312189.8
CHKB-CPT1B	ENST00000453634.5	n.*1584-6C>T		splice_region_variant, intron_variant	Intron 14 of 22	5		ENSP00000457031.1

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2954 AN: 152218 Hom.: 85 Cov.: 33

Gnomad AFR AF: 0.0670

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00572 AC: 1412 AN: 246642 AF XY: 0.00418

Gnomad AFR exome AF: 0.0709

Gnomad AMR exome AF: 0.00430

Gnomad ASJ exome AF: 0.00774

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000283

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00230 AC: 3335 AN: 1449750 Hom.: 99 Cov.: 30 AF XY: 0.00198 AC XY: 1427 AN XY: 721880

African (AFR) AF: 0.0729 AC: 2420 AN: 33214

American (AMR) AF: 0.00502 AC: 224 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.00638 AC: 166 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.000151 AC: 13 AN: 85972

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53122

Middle Eastern (MID) AF: 0.00419 AC: 24 AN: 5734

European-Non Finnish (NFE) AF: 0.000166 AC: 183 AN: 1101422

Other (OTH) AF: 0.00507 AC: 304 AN: 60002

GnomAD4 genome AF: 0.0194 AC: 2961 AN: 152336 Hom.: 86 Cov.: 33 AF XY: 0.0183 AC XY: 1364 AN XY: 74488

African (AFR) AF: 0.0670 AC: 2783 AN: 41558

American (AMR) AF: 0.00732 AC: 112 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68038

Other (OTH) AF: 0.0156 AC: 33 AN: 2116

Alfa AF: 0.0111 Hom.: 20

Bravo AF: 0.0222

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000653

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 25, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.8
DANN	Benign	0.52
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000029
dbscSNV1_RF	Benign	0.0060
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: rs115830405; hg19: chr22-51010743;