rs2305095

Positions:

• chr11-27055430-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003986.3(BBOX1):​c.-1C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,611,712 control chromosomes in the GnomAD database, including 19,004 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 0.12 (1407 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17597 hom.)
• Consequence: BBOX1 NM_003986.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

Genes affected

BBOX1 (HGNC:964): (gamma-butyrobetaine hydroxylase 1) This gene encodes gamma butyrobetaine hydroxylase which catalyzes the formation of L-carnitine from gamma-butyrobetaine, the last step in the L-carnitine biosynthetic pathway. Carnitine is essential for the transport of activated fatty acids across the mitochondrial membrane during mitochondrial beta-oxidation. [provided by RefSeq, Jul 2008]

BBOX1-AS1 (HGNC:50700): (BBOX1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBOX1	NM_003986.3	c.-1C>T		5_prime_UTR_variant	3/9	ENST00000263182.8
BBOX1-AS1	NR_125768.1	n.378-8118G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBOX1	ENST00000263182.8	c.-1C>T		5_prime_UTR_variant	3/9	5	NM_003986.3	P1
BBOX1-AS1	ENST00000526061.5	n.345-8118G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17749 AN: 152072 Hom.: 1406 Cov.: 32

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.112

GnomAD3 exomes AF: 0.158 AC: 39561 AN: 250906 Hom.: 3791 AF XY: 0.154 AC XY: 20939 AN XY: 135614

Gnomad AFR exome AF: 0.0284

Gnomad AMR exome AF: 0.270

Gnomad ASJ exome AF: 0.110

Gnomad EAS exome AF: 0.289

Gnomad SAS exome AF: 0.144

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.150 AC: 218472 AN: 1459522 Hom.: 17597 Cov.: 31 AF XY: 0.149 AC XY: 108264 AN XY: 725966

Gnomad4 AFR exome AF: 0.0255

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.276

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.117 AC: 17753 AN: 152190 Hom.: 1407 Cov.: 32 AF XY: 0.119 AC XY: 8847 AN XY: 74390

Gnomad4 AFR AF: 0.0325

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.112

Alfa AF: 0.137 Hom.: 3646

Bravo AF: 0.123

Asia WGS AF: 0.180 AC: 625 AN: 3478

EpiCase AF: 0.132

EpiControl AF: 0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.79

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

Other links and lift over

dbSNP: rs2305095; hg19: chr11-27076977; COSMIC: COSV54191372;