15-78178692-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015162.5(ACSBG1):c.1624G>A(p.Glu542Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,614,020 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (8 hom.)
• Consequence: ACSBG1 NM_015162.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.11

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003442645).
• BP6: Variant 15-78178692-C-T is Benign according to our data. Variant chr15-78178692-C-T is described in ClinVar as [Benign]. Clinvar id is 709282.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00628 (957/152356) while in subpopulation AFR AF= 0.0212 (881/41586). AF 95% confidence interval is 0.02. There are 12 homozygotes in gnomad4. There are 442 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSBG1	NM_015162.5	c.1624G>A	p.Glu542Lys	missense_variant	11/14	ENST00000258873.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSBG1	ENST00000258873.9	c.1624G>A	p.Glu542Lys	missense_variant	11/14	1	NM_015162.5	P1
ACSBG1	ENST00000560817.5	c.898G>A	p.Glu300Lys	missense_variant	7/10	5
ACSBG1	ENST00000560124.5	c.*936G>A		3_prime_UTR_variant, NMD_transcript_variant	7/10	2

Frequencies

GnomAD3 genomes AF: 0.00627 AC: 955 AN: 152238 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00185 AC: 462 AN: 250382 Hom.: 1 AF XY: 0.00151 AC XY: 204 AN XY: 135486

Gnomad AFR exome AF: 0.0209

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000716

Gnomad OTH exome AF: 0.000982

GnomAD4 exome AF: 0.00114 AC: 1665 AN: 1461664 Hom.: 8 Cov.: 30 AF XY: 0.00101 AC XY: 737 AN XY: 727130

Gnomad4 AFR exome AF: 0.0223

Gnomad4 AMR exome AF: 0.00119

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000674

Gnomad4 OTH exome AF: 0.00174

GnomAD4 genome AF: 0.00628 AC: 957 AN: 152356 Hom.: 12 Cov.: 32 AF XY: 0.00593 AC XY: 442 AN XY: 74500

Gnomad4 AFR AF: 0.0212

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000720

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00167 Hom.: 4

Bravo AF: 0.00748

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0198 AC: 87

ESP6500EA AF: 0.000699 AC: 6

ExAC AF: 0.00209 AC: 254

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	12
Dann	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.69	D
LIST_S2	Pathogenic	0.97	D;D
MetaRNN	Benign	0.0034	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.3	N;D
REVEL	Benign	0.084
Sift	Benign	0.30	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.012	B;.
Vest4		0.11
MVP		0.48
MPC		0.38
ClinPred		0.012	T
GERP RS		1.2
Varity_R		0.13
gMVP		0.42

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: rs34921279; hg19: chr15-78471034;