chr20-34922859-A-G

Variant names:

• chr20-34922859-A-G
• rs6087649
• NM_018677.4:c.1549-464A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS2	NM_018677.4	MANE Select	c.1549-464A>G		intron	N/A	NP_061147.1
	ACSS2	NM_001076552.3		c.1588-464A>G		intron	N/A	NP_001070020.2
	ACSS2	NM_001242393.2		c.1264-464A>G		intron	N/A	NP_001229322.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSS2	ENST00000360596.7	TSL:1 MANE Select	c.1549-464A>G		intron	N/A	ENSP00000353804.2
	ACSS2	ENST00000494727.1	TSL:2	n.18A>G		non_coding_transcript_exon	Exon 1 of 5
	ACSS2	ENST00000253382.5	TSL:2	c.1588-464A>G		intron	N/A	ENSP00000253382.5

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

African (AFR) AF: 0.322 AC: 29 AN: 90

American (AMR) AF: 0.346 AC: 390 AN: 1126

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 55 AN: 86

East Asian (EAS) AF: 0.455 AC: 265 AN: 582

South Asian (SAS) AF: 0.727 AC: 413 AN: 568

European-Finnish (FIN) AF: 0.581 AC: 79 AN: 136

Middle Eastern (MID) AF: 0.875 AC: 7 AN: 8

European-Non Finnish (NFE) AF: 0.608 AC: 1824 AN: 3002

Other (OTH) AF: 0.631 AC: 140 AN: 222

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

African (AFR) AF: 0.457 AC: 18946 AN: 41424

American (AMR) AF: 0.424 AC: 6475 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2173 AN: 3472

East Asian (EAS) AF: 0.450 AC: 2318 AN: 5150

South Asian (SAS) AF: 0.736 AC: 3546 AN: 4820

European-Finnish (FIN) AF: 0.596 AC: 6282 AN: 10540

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

European-Non Finnish (NFE) AF: 0.612 AC: 41629 AN: 67980

Other (OTH) AF: 0.543 AC: 1143 AN: 2104

Alfa AF: 0.578 Hom.: 3874

Bravo AF: 0.523

Asia WGS AF: 0.596 AC: 2078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		0.33
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: rs6087649; hg19: chr20-33510662;