Genetic Variant NM_003986.3:c.621C>T (chr11-27115539-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_003986.3(BBOX1):c.621C>T(p.Ala207Ala) 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0140

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 11-27115539-C-T is Benign according to our data. Variant chr11-27115539-C-T is described in ClinVar as Benign. ClinVar VariationId is 780965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.014 with no splicing effect.

BS1

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003986.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BBOX1	NM_003986.3	MANE Select	c.621C>T	p.Ala207Ala	synonymous	Exon 6 of 9	NP_003977.1	O75936
BBOX1	NM_001376258.1		c.621C>T	p.Ala207Ala	synonymous	Exon 6 of 9	NP_001363187.1	O75936
BBOX1	NM_001376259.1		c.621C>T	p.Ala207Ala	synonymous	Exon 6 of 9	NP_001363188.1	O75936

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BBOX1	ENST00000263182.8	TSL:5 MANE Select	c.621C>T	p.Ala207Ala	synonymous	Exon 6 of 9	ENSP00000263182.3	O75936
BBOX1	ENST00000525090.1	TSL:1	c.621C>T	p.Ala207Ala	synonymous	Exon 4 of 7	ENSP00000433772.1	O75936
BBOX1	ENST00000528583.5	TSL:1	c.621C>T	p.Ala207Ala	synonymous	Exon 5 of 8	ENSP00000434918.1	O75936

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1827

AN:

151652

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00347

AC:

865

AN:

248942

AF XY:

0.00267

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 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.:

Cov.:

AF XY:

0.00147

AC XY:

1067

AN XY:

725444

show subpopulations

African (AFR)

AF:

0.0407

AC:

1350

AN:

33144

American (AMR)

AF:

0.00304

AC:

135

AN:

44374

Ashkenazi Jewish (ASJ)

AF:

0.00227

AC:

AN:

25990

East Asian (EAS)

AF:

0.00

AC:

AN:

39566

South Asian (SAS)

AF:

0.000186

AC:

AN:

86024

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53326

Middle Eastern (MID)

AF:

0.00418

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.000492

AC:

546

AN:

1109756

Other (OTH)

AF:

0.00311

AC:

187

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

109

218

328

437

546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0120

AC:

1826

AN:

151768

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

866

AN XY:

74160

show subpopulations

African (AFR)

AF:

0.0406

AC:

1686

AN:

41490

American (AMR)

AF:

0.00493

AC:

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.000210

AC:

AN:

4764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000605

AC:

AN:

67806

Other (OTH)

AF:

0.00810

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

179

269

358

448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00619

Hom.:

Bravo

AF:

0.0137

Asia WGS

AF:

0.00115

AC:

AN:

3476

EpiCase

AF:

0.000985

EpiControl

AF:

0.00108

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

5.6

(source)

DANN

Benign

0.78

PhyloP100

-0.014

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over