rs7238

Positions:

• chr22-50569059-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000312108.12(CPT1B):​c.*25T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 333,274 control chromosomes in the GnomAD database, including 9,182 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (7377 hom., cov: 32)
  • Exomes 𝑓: 0.11 (1805 hom.)
• Consequence: CPT1B ENST00000312108.12 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT1B	NM_152246.3	c.*25T>C		3_prime_UTR_variant	20/20	ENST00000312108.12	NP_689452.1
CHKB-CPT1B	NR_027928.2	n.4078T>C		non_coding_transcript_exon_variant	30/30
LOC107985568	XR_001755606.3	n.1060A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT1B	ENST00000312108.12	c.*25T>C		3_prime_UTR_variant	20/20	1	NM_152246.3	ENSP00000312189	P1
CPT1B	ENST00000405237.7	c.*25T>C		3_prime_UTR_variant	19/19	1		ENSP00000385486	P1
CPT1B	ENST00000395650.6			downstream_gene_variant		1		ENSP00000379011	P1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35636 AN: 151860 Hom.: 7355 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.0897

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.109 AC: 19725 AN: 181298 Hom.: 1805 Cov.: 0 AF XY: 0.110 AC XY: 10508 AN XY: 95250

Gnomad4 AFR exome AF: 0.552

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.0801

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.0816

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.235 AC: 35708 AN: 151976 Hom.: 7377 Cov.: 32 AF XY: 0.234 AC XY: 17400 AN XY: 74282

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.0934

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.0897

Gnomad4 OTH AF: 0.196

Alfa AF: 0.112 Hom.: 2010

Bravo AF: 0.253

Asia WGS AF: 0.173 AC: 604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs7238; hg19: chr22-51007488;