12-125070916-G-A

Position:

• chr12-125070916-G-A

Variant summary

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

The NM_023928.5(AACS):​c.134-2960G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,258 control chromosomes in the GnomAD database, including 1,888 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 0.14 (1888 hom., cov: 33)
• Consequence: AACS NM_023928.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39

Genes affected

AACS (HGNC:21298): (acetoacetyl-CoA synthetase) Predicted to enable acetoacetate-CoA ligase activity. Predicted to be involved in positive regulation of insulin secretion. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LOC105370052 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AACS	NM_023928.5	c.134-2960G>A		intron_variant		ENST00000316519.11
LOC105370052	XR_001749365.2	n.195-5806C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AACS	ENST00000316519.11	c.134-2960G>A		intron_variant		1	NM_023928.5	P1
AACS	ENST00000418937.6	c.134-2960G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21388 AN: 152140 Hom.: 1884 Cov.: 33

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.141

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.141 AC: 21410 AN: 152258 Hom.: 1888 Cov.: 33 AF XY: 0.150 AC XY: 11200 AN XY: 74442

Gnomad4 AFR AF: 0.0725

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0966 Hom.: 284

Bravo AF: 0.130

Asia WGS AF: 0.230 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.010
DANN	Benign	0.46

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: rs879993; hg19: chr12-125555462;