NM_015162.5:c.2076G>A

Variant names:

• chr15-78173606-C-T
• rs74894991
• NM_015162.5:c.2076G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_015162.5(ACSBG1):​c.2076G>A​(p.Ser692Ser) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.97
• Publications: 2 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 -16 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 VariationId is 718037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 42 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSBG1	NM_015162.5	MANE Select	c.2076G>A	p.Ser692Ser	synonymous	Exon 13 of 14	NP_055977.3
	ACSBG1	NM_001199377.2		c.2064G>A	p.Ser688Ser	synonymous	Exon 13 of 14	NP_001186306.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSBG1	ENST00000258873.9	TSL:1 MANE Select	c.2076G>A	p.Ser692Ser	synonymous	Exon 13 of 14	ENSP00000258873.4	Q96GR2
	ACSBG1	ENST00000889987.1		c.2118G>A	p.Ser706Ser	synonymous	Exon 13 of 14	ENSP00000560046.1
	ACSBG1	ENST00000889988.1		c.2061G>A	p.Ser687Ser	synonymous	Exon 13 of 14	ENSP00000560047.1

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

GnomAD2 exomes AF: 0.00363 AC: 911 AN: 251246 AF XY: 0.00271

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 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

African (AFR) AF: 0.0475 AC: 1589 AN: 33480

American (AMR) AF: 0.00226 AC: 101 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00467 AC: 122 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.0000827 AC: 92 AN: 1111986

Other (OTH) AF: 0.00310 AC: 187 AN: 60390

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

African (AFR) AF: 0.0475 AC: 1972 AN: 41532

American (AMR) AF: 0.00445 AC: 68 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68032

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00608 Hom.: 13

Bravo AF: 0.0148

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.85
PhyloP100		-3.0
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs74894991; hg19: chr15-78465948;