rs6114999

Positions:

• chr20-25007446-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.*316G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,194,314 control chromosomes in the GnomAD database, including 6,810 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 0.097 (802 hom., cov: 33)
  • Exomes 𝑓: 0.10 (6008 hom.)
• Consequence: ACSS1 NM_032501.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

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]

ACSS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSS1	NM_032501.4	c.*316G>A		3_prime_UTR_variant	14/14	ENST00000323482.9	NP_115890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSS1	ENST00000323482	c.*316G>A		3_prime_UTR_variant	14/14	1	NM_032501.4	ENSP00000316924.4
ACSS1	ENST00000484396.1	n.3553G>A		non_coding_transcript_exon_variant	2/2	1
ACSS1	ENST00000537502	c.*316G>A		3_prime_UTR_variant	13/13	2		ENSP00000439304.2
ACSS1	ENST00000432802.6	c.1663-521G>A		intron_variant		2		ENSP00000388793.2

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14818 AN: 152182 Hom.: 801 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0805

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0962

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.0929

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0936

GnomAD4 exome AF: 0.104 AC: 108849 AN: 1042014 Hom.: 6008 Cov.: 32 AF XY: 0.104 AC XY: 51149 AN XY: 492428

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0567

Gnomad4 ASJ exome AF: 0.0554

Gnomad4 EAS exome AF: 0.000684

Gnomad4 SAS exome AF: 0.0835

Gnomad4 FIN exome AF: 0.0683

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.0944

GnomAD4 genome AF: 0.0974 AC: 14833 AN: 152300 Hom.: 802 Cov.: 33 AF XY: 0.0937 AC XY: 6975 AN XY: 74470

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0803

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0959

Gnomad4 FIN AF: 0.0625

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0936

Alfa AF: 0.101 Hom.: 143

Bravo AF: 0.0985

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.68

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: rs6114999; hg19: chr20-24988082;