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GeneBe

11-27115539-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_003986.3(BBOX1):c.621C>T(p.Ala207=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,609,888 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 39 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 32 hom. )

Consequence

BBOX1
NM_003986.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0140
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-AS1 (HGNC:50700): (BBOX1 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.27).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-27115539-C-T is Benign according to our data. Variant chr11-27115539-C-T is described in ClinVar as [Benign]. Clinvar id is 780965.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.014 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1826/151768) while in subpopulation AFR AF= 0.0406 (1686/41490). AF 95% confidence interval is 0.039. There are 39 homozygotes in gnomad4. There are 866 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 39 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BBOX1NM_003986.3 linkuse as main transcriptc.621C>T p.Ala207= synonymous_variant 6/9 ENST00000263182.8
BBOX1-AS1NR_125768.1 linkuse as main transcriptn.377+35511G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BBOX1ENST00000263182.8 linkuse as main transcriptc.621C>T p.Ala207= synonymous_variant 6/95 NM_003986.3 P1
BBOX1-AS1ENST00000526061.5 linkuse as main transcriptn.344+35511G>A intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0120
AC:
1827
AN:
151652
Hom.:
39
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0408
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00494
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000210
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00637
Gnomad NFE
AF:
0.000605
Gnomad OTH
AF:
0.00819
GnomAD3 exomes
AF:
0.00347
AC:
865
AN:
248942
Hom.:
18
AF XY:
0.00267
AC XY:
359
AN XY:
134572
show subpopulations
Gnomad AFR exome
AF:
0.0405
Gnomad AMR exome
AF:
0.00250
Gnomad ASJ exome
AF:
0.00260
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000198
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000692
Gnomad OTH exome
AF:
0.00363
GnomAD4 exome
AF:
0.00159
AC:
2319
AN:
1458120
Hom.:
32
Cov.:
30
AF XY:
0.00147
AC XY:
1067
AN XY:
725444
show subpopulations
Gnomad4 AFR exome
AF:
0.0407
Gnomad4 AMR exome
AF:
0.00304
Gnomad4 ASJ exome
AF:
0.00227
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000186
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.000492
Gnomad4 OTH exome
AF:
0.00311
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0120
AC:
1826
AN:
151768
Hom.:
39
Cov.:
32
AF XY:
0.0117
AC XY:
866
AN XY:
74160
show subpopulations
Gnomad4 AFR
AF:
0.0406
Gnomad4 AMR
AF:
0.00493
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000210
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000605
Gnomad4 OTH
AF:
0.00810
Alfa
AF:
0.00601
Hom.:
10
Bravo
AF:
0.0137
Asia WGS
AF:
0.00115
AC:
4
AN:
3476
EpiCase
AF:
0.000985
EpiControl
AF:
0.00108

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.27
Cadd
Benign
5.6
Dann
Benign
0.78

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.

Other links and lift over

dbSNP: rs76937267; hg19: chr11-27137086; API