rs6138473

Positions:

• chr20-25031519-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032501.4(ACSS1):​c.432-561G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,134 control chromosomes in the GnomAD database, including 12,396 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (12396 hom., cov: 33)
• Consequence: ACSS1 NM_032501.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651

Genes affected

ACSS1 (HGNC:16091): (acyl-CoA synthetase short chain family member 1) This gene encodes a mitochondrial acetyl-CoA synthetase enzyme. A similar protein in mice plays an important role in the tricarboxylic acid cycle by catalyzing the conversion of acetate to acetyl CoA. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSS1	NM_032501.4	c.432-561G>A		intron_variant		ENST00000323482.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSS1	ENST00000323482.9	c.432-561G>A		intron_variant		1	NM_032501.4	P1
ACSS1	ENST00000432802.6	c.432-561G>A		intron_variant		2
ACSS1	ENST00000537502.5	c.69-561G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56455 AN: 152016 Hom.: 12367 Cov.: 33

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.371

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.372 AC: 56528 AN: 152134 Hom.: 12396 Cov.: 33 AF XY: 0.359 AC XY: 26700 AN XY: 74384

Gnomad4 AFR AF: 0.606

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.0878

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.369

Alfa AF: 0.340 Hom.: 1774

Bravo AF: 0.391

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.56

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: rs6138473; hg19: chr20-25012155;