20-25038463-G-A

Variant names:

• chr20-25038463-G-A
• rs6050267
• NM_032501.4:c.432-7505C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032501.4(ACSS1):​c.432-7505C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,208 control chromosomes in the GnomAD database, including 3,322 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 0.17 (3322 hom., cov: 33)
• Consequence: ACSS1 NM_032501.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032501.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS1	NM_032501.4	MANE Select	c.432-7505C>T		intron	N/A	NP_115890.2
	ACSS1	NM_001252675.2		c.432-7505C>T		intron	N/A	NP_001239604.1
	ACSS1	NM_001252677.2		c.432-7505C>T		intron	N/A	NP_001239606.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS1	ENST00000323482.9	TSL:1 MANE Select	c.432-7505C>T		intron	N/A	ENSP00000316924.4
	ACSS1	ENST00000432802.6	TSL:2	c.432-7505C>T		intron	N/A	ENSP00000388793.2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25897 AN: 152090 Hom.: 3316 Cov.: 33

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0654

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0779

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.170 AC: 25942 AN: 152208 Hom.: 3322 Cov.: 33 AF XY: 0.166 AC XY: 12321 AN XY: 74436

African (AFR) AF: 0.352 AC: 14618 AN: 41488

American (AMR) AF: 0.109 AC: 1666 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0654 AC: 227 AN: 3470

East Asian (EAS) AF: 0.0127 AC: 66 AN: 5182

South Asian (SAS) AF: 0.116 AC: 558 AN: 4818

European-Finnish (FIN) AF: 0.0779 AC: 828 AN: 10626

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7576 AN: 67996

Other (OTH) AF: 0.153 AC: 324 AN: 2116

Alfa AF: 0.136 Hom.: 1367

Bravo AF: 0.179

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.50
DANN	Benign	0.66
PhyloP100		-1.2
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: rs6050267; hg19: chr20-25019099;