15-78173606-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_015162.5(ACSBG1):c.2076G>A(p.Ser692=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,614,102 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (42 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (34 hom.)
• Consequence: ACSBG1 NM_015162.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.97

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 -10 ACMG points.

• BP6: Variant 15-78173606-C-T is Benign according to our data. Variant chr15-78173606-C-T is described in ClinVar as [Benign]. Clinvar id is 718037.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (2080/152276) while in subpopulation AFR AF= 0.0475 (1972/41532). AF 95% confidence interval is 0.0457. There are 42 homozygotes in gnomad4. There are 988 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSBG1	NM_015162.5	c.2076G>A	p.Ser692=	synonymous_variant	13/14	ENST00000258873.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSBG1	ENST00000258873.9	c.2076G>A	p.Ser692=	synonymous_variant	13/14	1	NM_015162.5	P1
ACSBG1	ENST00000560817.5	c.1350G>A	p.Ser450=	synonymous_variant	9/10	5
ACSBG1	ENST00000560183.1	n.662G>A		non_coding_transcript_exon_variant	2/2	2
ACSBG1	ENST00000560124.5	c.*1388G>A		3_prime_UTR_variant, NMD_transcript_variant	9/10	2

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2077 AN: 152158 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.0475

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00363 AC: 911 AN: 251246 Hom.: 17 AF XY: 0.00271 AC XY: 368 AN XY: 135826

Gnomad AFR exome AF: 0.0482

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.00367

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00144 AC: 2105 AN: 1461826 Hom.: 34 Cov.: 30 AF XY: 0.00121 AC XY: 877 AN XY: 727208

Gnomad4 AFR exome AF: 0.0475

Gnomad4 AMR exome AF: 0.00226

Gnomad4 ASJ exome AF: 0.00467

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000827

Gnomad4 OTH exome AF: 0.00310

GnomAD4 genome AF: 0.0137 AC: 2080 AN: 152276 Hom.: 42 Cov.: 32 AF XY: 0.0133 AC XY: 988 AN XY: 74474

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00581 Hom.: 10

Bravo AF: 0.0148

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000327

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.5
Dann	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.43		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.43		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs74894991; hg19: chr15-78465948;