rs2304824

Positions:

• chr15-78173785-T-C
• chr15-78173785-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015162.5(ACSBG1):​c.1897A>G​(p.Met633Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,613,758 control chromosomes in the GnomAD database, including 204,881 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.54 (23374 hom., cov: 32)
  • Exomes 𝑓: 0.50 (181507 hom.)
• Consequence: ACSBG1 NM_015162.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827

Genes affected

ACSBG1 (HGNC:29567): (acyl-CoA synthetase bubblegum family member 1) The protein encoded by this gene possesses long-chain acyl-CoA synthetase activity. It is thought to play a central role in brain very long-chain fatty acids metabolism and myelinogenesis. [provided by RefSeq, Jul 2008]

ACSBG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.0677799E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSBG1	NM_015162.5	c.1897A>G	p.Met633Val	missense_variant	13/14	ENST00000258873.9	NP_055977.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSBG1	ENST00000258873.9	c.1897A>G	p.Met633Val	missense_variant	13/14	1	NM_015162.5	ENSP00000258873.4

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82524 AN: 151910 Hom.: 23356 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.515

GnomAD3 exomes AF: 0.494 AC: 123878 AN: 251018 Hom.: 31509 AF XY: 0.500 AC XY: 67780 AN XY: 135662

Gnomad AFR exome AF: 0.694

Gnomad AMR exome AF: 0.399

Gnomad ASJ exome AF: 0.545

Gnomad EAS exome AF: 0.304

Gnomad SAS exome AF: 0.580

Gnomad FIN exome AF: 0.477

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.482

GnomAD4 exome AF: 0.495 AC: 723984 AN: 1461732 Hom.: 181507 Cov.: 55 AF XY: 0.498 AC XY: 361939 AN XY: 727160

Gnomad4 AFR exome AF: 0.701

Gnomad4 AMR exome AF: 0.407

Gnomad4 ASJ exome AF: 0.542

Gnomad4 EAS exome AF: 0.299

Gnomad4 SAS exome AF: 0.579

Gnomad4 FIN exome AF: 0.483

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.499

GnomAD4 genome AF: 0.543 AC: 82585 AN: 152026 Hom.: 23374 Cov.: 32 AF XY: 0.540 AC XY: 40093 AN XY: 74308

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.514

Alfa AF: 0.503 Hom.: 47829

Bravo AF: 0.544

TwinsUK AF: 0.506 AC: 1878

ALSPAC AF: 0.485 AC: 1870

ESP6500AA AF: 0.688 AC: 3021

ESP6500EA AF: 0.500 AC: 4289

ExAC AF: 0.502 AC: 60914

Asia WGS AF: 0.463 AC: 1612 AN: 3478

EpiCase AF: 0.498

EpiControl AF: 0.499

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.58
DANN	Benign	0.64
DEOGEN2	Benign	0.068	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.070	T;T
MetaRNN	Benign	0.0000021	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.7	N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	1.4	N;N
REVEL	Benign	0.054
Sift	Benign	0.73	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.0	B;.
Vest4		0.055
MPC		0.33
ClinPred		0.0027	T
GERP RS		-0.040
Varity_R		0.037
gMVP		0.50

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

Other links and lift over

dbSNP: rs2304824; hg19: chr15-78466127; COSMIC: COSV51906639; COSMIC: COSV51906639;