chr20-25031519-C-T

Variant names:

• chr20-25031519-C-T
• rs6138473
• NM_032501.4:c.432-561G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ACSS1	NM_032501.4	c.432-561G>A		intron_variant	Intron 2 of 13	ENST00000323482.9	NP_115890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSS1	ENST00000323482.9	c.432-561G>A		intron_variant	Intron 2 of 13	1	NM_032501.4	ENSP00000316924.4
ACSS1	ENST00000432802.6	c.432-561G>A		intron_variant	Intron 2 of 11	2		ENSP00000388793.2
ACSS1	ENST00000537502.5	c.69-561G>A		intron_variant	Intron 1 of 12	2		ENSP00000439304.2

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

African (AFR) AF: 0.606 AC: 25141 AN: 41486

American (AMR) AF: 0.285 AC: 4359 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1082 AN: 3470

East Asian (EAS) AF: 0.0878 AC: 455 AN: 5184

South Asian (SAS) AF: 0.207 AC: 1000 AN: 4822

European-Finnish (FIN) AF: 0.156 AC: 1657 AN: 10600

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21548 AN: 67976

Other (OTH) AF: 0.369 AC: 781 AN: 2114

Alfa AF: 0.347 Hom.: 1917

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
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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: rs6138473; hg19: chr20-25012155;