15-78173785-T-C

Variant names:

• chr15-78173785-T-C
• rs2304824
• NM_015162.5:c.1897A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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 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
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015162.5. 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
	ACSBG1	NM_015162.5	MANE Select	c.1897A>G	p.Met633Val	missense	Exon 13 of 14	NP_055977.3
	ACSBG1	NM_001199377.2		c.1885A>G	p.Met629Val	missense	Exon 13 of 14	NP_001186306.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSBG1	ENST00000258873.9	TSL:1 MANE Select	c.1897A>G	p.Met633Val	missense	Exon 13 of 14	ENSP00000258873.4
	ACSBG1	ENST00000560817.5	TSL:5	c.1171A>G	p.Met391Val	missense	Exon 9 of 10	ENSP00000453451.1
	ACSBG1	ENST00000560124.5	TSL:2	n.*1209A>G		non_coding_transcript_exon	Exon 9 of 10	ENSP00000453605.1

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

GnomAD2 exomes AF: 0.494 AC: 123878 AN: 251018 AF XY: 0.500

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 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

African (AFR) AF: 0.701 AC: 23457 AN: 33478

American (AMR) AF: 0.407 AC: 18211 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 14160 AN: 26134

East Asian (EAS) AF: 0.299 AC: 11875 AN: 39696

South Asian (SAS) AF: 0.579 AC: 49886 AN: 86232

European-Finnish (FIN) AF: 0.483 AC: 25814 AN: 53408

Middle Eastern (MID) AF: 0.546 AC: 3149 AN: 5768

European-Non Finnish (NFE) AF: 0.492 AC: 547279 AN: 1111920

Other (OTH) AF: 0.499 AC: 30153 AN: 60382

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

African (AFR) AF: 0.692 AC: 28704 AN: 41464

American (AMR) AF: 0.444 AC: 6784 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1870 AN: 3468

East Asian (EAS) AF: 0.297 AC: 1541 AN: 5182

South Asian (SAS) AF: 0.570 AC: 2741 AN: 4806

European-Finnish (FIN) AF: 0.489 AC: 5153 AN: 10540

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.500 AC: 34017 AN: 67970

Other (OTH) AF: 0.514 AC: 1085 AN: 2112

Alfa AF: 0.511 Hom.: 68291

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 v4.9

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
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.070	T
MetaRNN	Benign	0.0000021	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.7	N
PhyloP100		-0.83
PrimateAI	Benign	0.23	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.054
Sift	Benign	0.73	T
Sift4G	Benign	0.48	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
Mutation Taster		=100/0	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: rs2304824; hg19: chr15-78466127; COSMIC: COSV51906639; COSMIC: COSV51906639;