rs7942200

chr11-27092991-G-A

Variant summary

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

The NM_003986.3(BBOX1):c.335-177G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 151,974 control chromosomes in the GnomAD database, including 239 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 0.045 (239 hom., cov: 32)
• Consequence: BBOX1 NM_003986.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBOX1	NM_003986.3	c.335-177G>A		intron_variant		ENST00000263182.8
BBOX1-AS1	NR_125768.1	n.378-45679C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBOX1	ENST00000263182.8	c.335-177G>A		intron_variant		5	NM_003986.3	P1
BBOX1-AS1	ENST00000526061.5	n.345-45679C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6842 AN: 151856 Hom.: 238 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0498

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.0408

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0451 AC: 6847 AN: 151974 Hom.: 239 Cov.: 32 AF XY: 0.0446 AC XY: 3313 AN XY: 74278

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.0502

Gnomad4 ASJ AF: 0.0398

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0357

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0680

Gnomad4 OTH AF: 0.0404

Alfa AF: 0.0602 Hom.: 149

Bravo AF: 0.0436

Asia WGS AF: 0.0180 AC: 62 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.34
Dann	Benign	0.24

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: rs7942200; hg19: chr11-27114538;