Variant 11-27125777-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_003986.3(BBOX1):c.960C>A(p.Leu320=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,613,042 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 9 hom. )

Consequence

BBOX1
NM_003986.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.307

Variant links:

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 links:

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

BBOX1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 11-27125777-C-A is Benign according to our data. Variant chr11-27125777-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3035182.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.307 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBOX1	NM_003986.3 linkuse as main transcript	c.960C>A	p.Leu320=	synonymous_variant	8/9	ENST00000263182.8
BBOX1-AS1	NR_125768.1 linkuse as main transcript	n.377+25273G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBOX1	ENST00000263182.8 linkuse as main transcript	c.960C>A	p.Leu320=	synonymous_variant	8/9	5	NM_003986.3	P1
BBOX1-AS1	ENST00000526061.5 linkuse as main transcript	n.344+25273G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00189

AC:

288

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000850

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00310

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00227

AC:

562

AN:

247860

Hom.:

AF XY:

0.00247

AC XY:

332

AN XY:

134150

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.000598

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00198

Gnomad FIN exome

AF:

0.00231

Gnomad NFE exome

AF:

0.00343

Gnomad OTH exome

AF:

0.00263

GnomAD4 exome

AF:

0.00342

AC:

4996

AN:

1460766

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

2469

AN XY:

726610

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00128

Gnomad4 ASJ exome

AF:

0.000805

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00185

Gnomad4 FIN exome

AF:

0.00200

Gnomad4 NFE exome

AF:

0.00402

Gnomad4 OTH exome

AF:

0.00275

GnomAD4 genome

AF:

0.00189

AC:

288

AN:

152276

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000850

Gnomad4 NFE

AF:

0.00310

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00273

Hom.:

Bravo

AF:

0.00221

EpiCase

AF:

0.00284

EpiControl

AF:

0.00231

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

BBOX1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 25, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

4.8

DANN

Benign

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over