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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M633T) has been classified as Uncertain significance.

• 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]

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	UniProt
ACSBG1	NM_015162.5	c.1897A>G	p.Met633Val	missense_variant	13/14	ENST00000258873.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSBG1	ENST00000258873.9	c.1897A>G	p.Met633Val	missense_variant	13/14	1	NM_015162.5	P1
ACSBG1	ENST00000560817.5	c.1171A>G	p.Met391Val	missense_variant	9/10	5
ACSBG1	ENST00000560183.1	n.483A>G		non_coding_transcript_exon_variant	2/2	2
ACSBG1	ENST00000560124.5	c.*1209A>G		3_prime_UTR_variant, NMD_transcript_variant	9/10	2

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;.
MutationTaster	Benign	1.0	P;P;P
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;