20-34882891-C-T

Variant names:

• chr20-34882891-C-T
• rs4911163
• NM_018677.4:c.276C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_018677.4(ACSS2):​c.276C>T​(p.Phe92Phe) 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
• Publications: 42 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS2	NM_018677.4	MANE Select	c.276C>T	p.Phe92Phe	synonymous	Exon 2 of 18	NP_061147.1	Q9NR19-1
	ACSS2	NM_001076552.3		c.276C>T	p.Phe92Phe	synonymous	Exon 2 of 19	NP_001070020.2	Q9NR19-2
	ACSS2	NM_001242393.2		c.-10C>T		5_prime_UTR	Exon 2 of 18	NP_001229322.1	Q4G0E8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS2	ENST00000360596.7	TSL:1 MANE Select	c.276C>T	p.Phe92Phe	synonymous	Exon 2 of 18	ENSP00000353804.2	Q9NR19-1
	ACSS2	ENST00000484354.1	TSL:5	c.252C>T	p.Phe84Phe	synonymous	Exon 2 of 3	ENSP00000419167.1	C9JXD9
	ACSS2	ENST00000871370.1		c.276C>T	p.Phe92Phe	synonymous	Exon 2 of 20	ENSP00000541429.1

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

GnomAD2 exomes AF: 0.565 AC: 141629 AN: 250606 AF XY: 0.585

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 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

African (AFR) AF: 0.444 AC: 14838 AN: 33422

American (AMR) AF: 0.298 AC: 13303 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 16494 AN: 26110

East Asian (EAS) AF: 0.441 AC: 17502 AN: 39652

South Asian (SAS) AF: 0.738 AC: 63564 AN: 86076

European-Finnish (FIN) AF: 0.604 AC: 32249 AN: 53418

Middle Eastern (MID) AF: 0.608 AC: 3509 AN: 5768

European-Non Finnish (NFE) AF: 0.621 AC: 690011 AN: 1111578

Other (OTH) AF: 0.601 AC: 36281 AN: 60352

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

African (AFR) AF: 0.442 AC: 18297 AN: 41412

American (AMR) AF: 0.422 AC: 6451 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2169 AN: 3472

East Asian (EAS) AF: 0.450 AC: 2328 AN: 5178

South Asian (SAS) AF: 0.733 AC: 3521 AN: 4806

European-Finnish (FIN) AF: 0.595 AC: 6278 AN: 10550

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41587 AN: 67966

Other (OTH) AF: 0.540 AC: 1140 AN: 2112

Alfa AF: 0.589 Hom.: 130855

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Benign	0.66
PhyloP100		0.71
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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