chr11-27093232-T-C

Variant names:

• chr11-27093232-T-C
• rs143972595
• NM_003986.3:c.399T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_003986.3(BBOX1):​c.399T>C​(p.Tyr133Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 1,612,522 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (1 hom.)
• Consequence: BBOX1 NM_003986.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.849
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-27093232-T-C is Benign according to our data. Variant chr11-27093232-T-C is described in ClinVar as Benign. ClinVar VariationId is 735727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.849 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBOX1	NM_003986.3	MANE Select	c.399T>C	p.Tyr133Tyr	synonymous	Exon 5 of 9	NP_003977.1	O75936
	BBOX1	NM_001376258.1		c.399T>C	p.Tyr133Tyr	synonymous	Exon 5 of 9	NP_001363187.1	O75936
	BBOX1	NM_001376259.1		c.399T>C	p.Tyr133Tyr	synonymous	Exon 5 of 9	NP_001363188.1	O75936

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBOX1	ENST00000263182.8	TSL:5 MANE Select	c.399T>C	p.Tyr133Tyr	synonymous	Exon 5 of 9	ENSP00000263182.3	O75936
	BBOX1	ENST00000525090.1	TSL:1	c.399T>C	p.Tyr133Tyr	synonymous	Exon 3 of 7	ENSP00000433772.1	O75936
	BBOX1	ENST00000528583.5	TSL:1	c.399T>C	p.Tyr133Tyr	synonymous	Exon 4 of 8	ENSP00000434918.1	O75936

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 262 AN: 151930 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00587

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000412 AC: 103 AN: 250166 AF XY: 0.000340

Gnomad AFR exome AF: 0.00500

Gnomad AMR exome AF: 0.000494

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000187 AC: 273 AN: 1460474 Hom.: 1 Cov.: 30 AF XY: 0.000151 AC XY: 110 AN XY: 726566

African (AFR) AF: 0.00659 AC: 220 AN: 33384

American (AMR) AF: 0.000516 AC: 23 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111102

Other (OTH) AF: 0.000431 AC: 26 AN: 60306

GnomAD4 genome AF: 0.00175 AC: 266 AN: 152048 Hom.: 0 Cov.: 32 AF XY: 0.00192 AC XY: 143 AN XY: 74310

African (AFR) AF: 0.00595 AC: 247 AN: 41520

American (AMR) AF: 0.00105 AC: 16 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67926

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.00240 Hom.: 0

Bravo AF: 0.00191

Asia WGS AF: 0.000289 AC: 1 AN: 3476

EpiCase AF: 0.0000546

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.63
DANN	Benign	0.39
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs143972595; hg19: chr11-27114779;