11-27055430-C-T

Variant names:

• chr11-27055430-C-T
• rs2305095
• NM_003986.3:c.-1C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003986.3(BBOX1):​c.-1C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,611,712 control chromosomes in the GnomAD database, including 19,004 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 0.12 (1407 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17597 hom.)
• Consequence: BBOX1 NM_003986.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBOX1	NM_003986.3	MANE Select	c.-1C>T		5_prime_UTR	Exon 3 of 9	NP_003977.1
	BBOX1	NM_001376258.1		c.-1C>T		5_prime_UTR	Exon 3 of 9	NP_001363187.1
	BBOX1	NM_001376259.1		c.-1C>T		5_prime_UTR	Exon 3 of 9	NP_001363188.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBOX1	ENST00000263182.8	TSL:5 MANE Select	c.-1C>T		5_prime_UTR	Exon 3 of 9	ENSP00000263182.3
	BBOX1	ENST00000525090.1	TSL:1	c.-1C>T		5_prime_UTR	Exon 1 of 7	ENSP00000433772.1
	BBOX1	ENST00000528583.5	TSL:1	c.-1C>T		5_prime_UTR	Exon 2 of 8	ENSP00000434918.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17749 AN: 152072 Hom.: 1406 Cov.: 32

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.158 AC: 39561 AN: 250906 AF XY: 0.154

Gnomad AFR exome AF: 0.0284

Gnomad AMR exome AF: 0.270

Gnomad ASJ exome AF: 0.110

Gnomad EAS exome AF: 0.289

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.150 AC: 218472 AN: 1459522 Hom.: 17597 Cov.: 31 AF XY: 0.149 AC XY: 108264 AN XY: 725966

African (AFR) AF: 0.0255 AC: 853 AN: 33424

American (AMR) AF: 0.266 AC: 11903 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 2751 AN: 26106

East Asian (EAS) AF: 0.276 AC: 10951 AN: 39666

South Asian (SAS) AF: 0.145 AC: 12461 AN: 86170

European-Finnish (FIN) AF: 0.116 AC: 6209 AN: 53378

Middle Eastern (MID) AF: 0.0710 AC: 361 AN: 5084

European-Non Finnish (NFE) AF: 0.148 AC: 164509 AN: 1110764

Other (OTH) AF: 0.141 AC: 8474 AN: 60246

GnomAD4 genome AF: 0.117 AC: 17753 AN: 152190 Hom.: 1407 Cov.: 32 AF XY: 0.119 AC XY: 8847 AN XY: 74390

African (AFR) AF: 0.0325 AC: 1350 AN: 41556

American (AMR) AF: 0.193 AC: 2949 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3472

East Asian (EAS) AF: 0.271 AC: 1398 AN: 5160

South Asian (SAS) AF: 0.140 AC: 674 AN: 4814

European-Finnish (FIN) AF: 0.117 AC: 1236 AN: 10570

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9387 AN: 68022

Other (OTH) AF: 0.112 AC: 237 AN: 2108

Alfa AF: 0.133 Hom.: 5276

Bravo AF: 0.123

Asia WGS AF: 0.180 AC: 625 AN: 3478

EpiCase AF: 0.132

EpiControl AF: 0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		1.6
PromoterAI		-0.036	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs2305095; hg19: chr11-27076977; COSMIC: COSV54191372;