chr15-78173669-G-A

Variant names:

• chr15-78173669-G-A
• rs138480953
• NM_015162.5:c.2013C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_015162.5(ACSBG1):​c.2013C>T​(p.Asn671Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,614,194 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (18 hom.)
• Consequence: ACSBG1 NM_015162.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.54
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 15-78173669-G-A is Benign according to our data. Variant chr15-78173669-G-A is described in ClinVar as Benign. ClinVar VariationId is 785502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.54 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00726 (1106/152308) while in subpopulation AFR AF = 0.0256 (1064/41568). AF 95% confidence interval is 0.0243. There are 15 homozygotes in GnomAd4. There are 520 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 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.2013C>T	p.Asn671Asn	synonymous	Exon 13 of 14	NP_055977.3
	ACSBG1	NM_001199377.2		c.2001C>T	p.Asn667Asn	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.2013C>T	p.Asn671Asn	synonymous	Exon 13 of 14	ENSP00000258873.4	Q96GR2
	ACSBG1	ENST00000889987.1		c.2055C>T	p.Asn685Asn	synonymous	Exon 13 of 14	ENSP00000560046.1
	ACSBG1	ENST00000889988.1		c.1998C>T	p.Asn666Asn	synonymous	Exon 13 of 14	ENSP00000560047.1

Frequencies

GnomAD3 genomes AF: 0.00726 AC: 1105 AN: 152190 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00188 AC: 472 AN: 251486 AF XY: 0.00152

Gnomad AFR exome AF: 0.0255

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000105

Gnomad OTH exome AF: 0.000814

GnomAD4 exome AF: 0.000810 AC: 1184 AN: 1461886 Hom.: 18 Cov.: 31 AF XY: 0.000704 AC XY: 512 AN XY: 727246

African (AFR) AF: 0.0282 AC: 944 AN: 33478

American (AMR) AF: 0.00125 AC: 56 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.0000629 AC: 70 AN: 1112010

Other (OTH) AF: 0.00161 AC: 97 AN: 60396

GnomAD4 genome AF: 0.00726 AC: 1106 AN: 152308 Hom.: 15 Cov.: 32 AF XY: 0.00698 AC XY: 520 AN XY: 74474

African (AFR) AF: 0.0256 AC: 1064 AN: 41568

American (AMR) AF: 0.00176 AC: 27 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00331 Hom.: 1

Bravo AF: 0.00835

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000178

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	-0.92
CADD	Benign	0.086
DANN	Benign	0.88
PhyloP100		-4.5
Mutation Taster		=99/1	polymorphism

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: rs138480953; hg19: chr15-78466011;