rs41309651

Variant names:

• chr22-50571058-T-C
• rs41309651
• NM_152246.3:c.1876-15A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_152246.3(CPT1B):​c.1876-15A>G variant causes a 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0095 (12 hom., cov: 33)
  • Exomes 𝑓: 0.015 (240 hom.)
• Consequence: CPT1B NM_152246.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -2.44
• Publications: 3 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 -14 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 Benign. ClinVar VariationId is 1285039.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152246.3. 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
	CPT1B	NM_152246.3	MANE Select	c.1876-15A>G		intron	N/A	NP_689452.1	Q92523-1
	CPT1B	NM_001145135.2		c.1876-15A>G		intron	N/A	NP_001138607.1	Q92523-1
	CPT1B	NM_001145137.2		c.1876-15A>G		intron	N/A	NP_001138609.1	Q92523-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1B	ENST00000312108.12	TSL:1 MANE Select	c.1876-15A>G		intron	N/A	ENSP00000312189.8	Q92523-1
	CPT1B	ENST00000395650.6	TSL:1	c.1876-15A>G		intron	N/A	ENSP00000379011.2	Q92523-1
	CPT1B	ENST00000405237.7	TSL:1	c.1876-15A>G		intron	N/A	ENSP00000385486.3	Q92523-1

Frequencies

GnomAD3 genomes AF: 0.00950 AC: 1444 AN: 152068 Hom.: 12 Cov.: 33

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

GnomAD2 exomes AF: 0.00990 AC: 2464 AN: 248888 AF XY: 0.0101

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 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.: 32 AF XY: 0.0148 AC XY: 10754 AN XY: 726762

African (AFR) AF: 0.00281 AC: 94 AN: 33466

American (AMR) AF: 0.00277 AC: 124 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00356 AC: 93 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.000846 AC: 73 AN: 86252

European-Finnish (FIN) AF: 0.0112 AC: 598 AN: 53256

Middle Eastern (MID) AF: 0.00572 AC: 33 AN: 5766

European-Non Finnish (NFE) AF: 0.0183 AC: 20305 AN: 1111552

Other (OTH) AF: 0.0114 AC: 691 AN: 60364

GnomAD4 genome AF: 0.00949 AC: 1444 AN: 152186 Hom.: 12 Cov.: 33 AF XY: 0.00919 AC XY: 684 AN XY: 74406

African (AFR) AF: 0.00226 AC: 94 AN: 41526

American (AMR) AF: 0.00392 AC: 60 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4822

European-Finnish (FIN) AF: 0.00934 AC: 99 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0170 AC: 1157 AN: 67992

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.0116 Hom.: 2

Bravo AF: 0.00890

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0090
DANN	Benign	0.48
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism

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: rs41309651; hg19: chr22-51009487;