20-34882891-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_018677.4(ACSS2):c.276C>T(p.Phe92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,612,964 control chromosomes in the GnomAD database, including 297,373 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 0.54 (23074 hom., cov: 32)
  • Exomes 𝑓: 0.61 (274299 hom.)
• Consequence: ACSS2 NM_018677.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.707

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=0.707 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSS2	NM_018677.4	c.276C>T	p.Phe92=	synonymous_variant	2/18	ENST00000360596.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSS2	ENST00000360596.7	c.276C>T	p.Phe92=	synonymous_variant	2/18	1	NM_018677.4	P4

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82353 AN: 151862 Hom.: 23061 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.535

GnomAD3 exomes AF: 0.565 AC: 141629 AN: 250606 Hom.: 42552 AF XY: 0.585 AC XY: 79277 AN XY: 135480

Gnomad AFR exome AF: 0.450

Gnomad AMR exome AF: 0.281

Gnomad ASJ exome AF: 0.631

Gnomad EAS exome AF: 0.481

Gnomad SAS exome AF: 0.739

Gnomad FIN exome AF: 0.608

Gnomad NFE exome AF: 0.620

Gnomad OTH exome AF: 0.575

GnomAD4 exome AF: 0.608 AC: 887751 AN: 1460984 Hom.: 274299 Cov.: 44 AF XY: 0.613 AC XY: 445496 AN XY: 726788

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.298

Gnomad4 ASJ exome AF: 0.632

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.738

Gnomad4 FIN exome AF: 0.604

Gnomad4 NFE exome AF: 0.621

Gnomad4 OTH exome AF: 0.601

GnomAD4 genome AF: 0.542 AC: 82375 AN: 151980 Hom.: 23074 Cov.: 32 AF XY: 0.541 AC XY: 40215 AN XY: 74284

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.540

Alfa AF: 0.597 Hom.: 68938

Bravo AF: 0.517

Asia WGS AF: 0.595 AC: 2073 AN: 3478

EpiCase AF: 0.614

EpiControl AF: 0.612

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	12
Dann	Benign	0.66
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

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: rs4911163; hg19: chr20-33470694; COSMIC: COSV53623170;