rs6132784

Positions:

• chr20-25007151-A-G

Variant summary

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

The NM_032501.4(ACSS1):​c.*611T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,320,066 control chromosomes in the GnomAD database, including 18,624 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 0.13 (1570 hom., cov: 33)
  • Exomes 𝑓: 0.17 (17054 hom.)
• Consequence: ACSS1 NM_032501.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSS1	NM_032501.4	c.*611T>C		3_prime_UTR_variant	14/14	ENST00000323482.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSS1	ENST00000323482.9	c.*611T>C		3_prime_UTR_variant	14/14	1	NM_032501.4	P1
ACSS1	ENST00000484396.1	n.3848T>C		non_coding_transcript_exon_variant	2/2	1
ACSS1	ENST00000537502.5	c.*611T>C		3_prime_UTR_variant	13/13	2
ACSS1	ENST00000432802.6	c.1663-226T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20508 AN: 152140 Hom.: 1572 Cov.: 33

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0641

Gnomad SAS AF: 0.0928

Gnomad FIN AF: 0.0868

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.168 AC: 196476 AN: 1167808 Hom.: 17054 Cov.: 32 AF XY: 0.167 AC XY: 93533 AN XY: 558990

Gnomad4 AFR exome AF: 0.0741

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.0701

Gnomad4 SAS exome AF: 0.0878

Gnomad4 FIN exome AF: 0.0989

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.135 AC: 20506 AN: 152258 Hom.: 1570 Cov.: 33 AF XY: 0.130 AC XY: 9662 AN XY: 74450

Gnomad4 AFR AF: 0.0782

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.0642

Gnomad4 SAS AF: 0.0935

Gnomad4 FIN AF: 0.0868

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.160

Alfa AF: 0.161 Hom.: 1270

Bravo AF: 0.134

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.9
DANN	Benign	0.72

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: rs6132784; hg19: chr20-24987787;