rs6050267

Positions:

• chr20-25038463-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSS1	NM_032501.4	c.432-7505C>T		intron_variant		ENST00000323482.9	NP_115890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSS1	ENST00000323482.9	c.432-7505C>T		intron_variant		1	NM_032501.4	ENSP00000316924	P1
ACSS1	ENST00000432802.6	c.432-7505C>T		intron_variant		2		ENSP00000388793

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

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0654

Gnomad4 EAS AF: 0.0127

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0779

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.153

Alfa AF: 0.124 Hom.: 799

Bravo AF: 0.179

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.50
DANN	Benign	0.66

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: rs6050267; hg19: chr20-25019099;