20-34920785-G-T

Position:

• chr20-34920785-G-T

Variant summary

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

The NM_018677.4(ACSS2):​c.1143+76G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,528,560 control chromosomes in the GnomAD database, including 282,696 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 (23366 hom., cov: 31)
  • Exomes 𝑓: 0.61 (259330 hom.)
• Consequence: ACSS2 NM_018677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171

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]

ACSS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• 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	Protein	UniProt
ACSS2	NM_018677.4	c.1143+76G>T		intron_variant		ENST00000360596.7	NP_061147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSS2	ENST00000360596.7	c.1143+76G>T		intron_variant		1	NM_018677.4	ENSP00000353804.2

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83018 AN: 151740 Hom.: 23355 Cov.: 31

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.609 AC: 838850 AN: 1376702 Hom.: 259330 Cov.: 24 AF XY: 0.614 AC XY: 416891 AN XY: 679122

Gnomad4 AFR exome AF: 0.460

Gnomad4 AMR exome AF: 0.304

Gnomad4 ASJ exome AF: 0.634

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.604

Gnomad4 NFE exome AF: 0.621

Gnomad4 OTH exome AF: 0.603

GnomAD4 genome AF: 0.547 AC: 83038 AN: 151858 Hom.: 23366 Cov.: 31 AF XY: 0.546 AC XY: 40538 AN XY: 74200

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.542

Alfa AF: 0.510 Hom.: 2031

Bravo AF: 0.523

Asia WGS AF: 0.596 AC: 2076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.7
DANN	Benign	0.73

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: rs3746450; hg19: chr20-33508588;