chr22-50569059-A-G

Variant names:

• chr22-50569059-A-G
• rs7238
• NM_152246.3:c.*25T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152246.3(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 NM_152246.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 7 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]

LOC107985568 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.*25T>C		3_prime_UTR	Exon 20 of 20	NP_689452.1	Q92523-1
	CPT1B	NM_001145135.2		c.*25T>C		3_prime_UTR	Exon 20 of 20	NP_001138607.1	Q92523-1
	CPT1B	NM_001145137.2		c.*25T>C		3_prime_UTR	Exon 19 of 19	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.*25T>C		3_prime_UTR	Exon 20 of 20	ENSP00000312189.8	Q92523-1
	CPT1B	ENST00000405237.7	TSL:1	c.*25T>C		3_prime_UTR	Exon 19 of 19	ENSP00000385486.3	Q92523-1
	CHKB-CPT1B	ENST00000453634.5	TSL:5	n.*2569T>C		non_coding_transcript_exon	Exon 23 of 23	ENSP00000457031.1	H3BT56

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

African (AFR) AF: 0.552 AC: 2472 AN: 4480

American (AMR) AF: 0.177 AC: 1153 AN: 6504

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 586 AN: 5802

East Asian (EAS) AF: 0.0801 AC: 875 AN: 10928

South Asian (SAS) AF: 0.138 AC: 2751 AN: 19934

European-Finnish (FIN) AF: 0.123 AC: 1245 AN: 10116

Middle Eastern (MID) AF: 0.145 AC: 123 AN: 848

European-Non Finnish (NFE) AF: 0.0816 AC: 9124 AN: 111868

Other (OTH) AF: 0.129 AC: 1396 AN: 10818

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

African (AFR) AF: 0.561 AC: 23216 AN: 41386

American (AMR) AF: 0.179 AC: 2734 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0934 AC: 324 AN: 3468

East Asian (EAS) AF: 0.113 AC: 584 AN: 5190

South Asian (SAS) AF: 0.151 AC: 728 AN: 4808

European-Finnish (FIN) AF: 0.145 AC: 1534 AN: 10546

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.0897 AC: 6100 AN: 67986

Other (OTH) AF: 0.196 AC: 414 AN: 2110

Alfa AF: 0.127 Hom.: 3515

Bravo AF: 0.253

Asia WGS AF: 0.173 AC: 604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.62
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7238; hg19: chr22-51007488;