rs6087649

Positions:

• chr20-34922859-A-G
• chr20-34922859-A-T

Variant summary

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

The NM_018677.4(ACSS2):​c.1549-464A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 157,766 control chromosomes in the GnomAD database, including 24,354 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 0.55 (23399 hom., cov: 32)
  • Exomes 𝑓: 0.55 (955 hom.)
• Consequence: ACSS2 NM_018677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334

Genes affected

ACSS2 (HGNC:15814): (acyl-CoA synthetase short chain family member 2) This gene encodes a cytosolic enzyme that catalyzes the activation of acetate for use in lipid synthesis and energy generation. The protein acts as a monomer and produces acetyl-CoA from acetate in a reaction that requires ATP. Expression of this gene is regulated by sterol regulatory element-binding proteins, transcription factors that activate genes required for the synthesis of cholesterol and unsaturated fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSS2	NM_018677.4	c.1549-464A>G		intron_variant		ENST00000360596.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSS2	ENST00000360596.7	c.1549-464A>G		intron_variant		1	NM_018677.4	P4

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83092 AN: 151828 Hom.: 23388 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.538

GnomAD4 exome AF: 0.550 AC: 3202 AN: 5820 Hom.: 955 Cov.: 0 AF XY: 0.559 AC XY: 1756 AN XY: 3144

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.640

Gnomad4 EAS exome AF: 0.455

Gnomad4 SAS exome AF: 0.727

Gnomad4 FIN exome AF: 0.581

Gnomad4 NFE exome AF: 0.608

Gnomad4 OTH exome AF: 0.631

GnomAD4 genome AF: 0.547 AC: 83112 AN: 151946 Hom.: 23399 Cov.: 32 AF XY: 0.547 AC XY: 40593 AN XY: 74270

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.543

Alfa AF: 0.580 Hom.: 3779

Bravo AF: 0.523

Asia WGS AF: 0.596 AC: 2078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.86

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: rs6087649; hg19: chr20-33510662;