18-49790623-A-G

Position:

• chr18-49790623-A-G

Variant summary

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

The NM_006111.3(ACAA2):​c.883+847T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,004 control chromosomes in the GnomAD database, including 27,444 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 0.60 (27444 hom., cov: 32)
• Consequence: ACAA2 NM_006111.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

Genes affected

ACAA2 (HGNC:83): (acetyl-CoA acyltransferase 2) The encoded protein catalyzes the last step of the mitochondrial fatty acid beta-oxidation spiral. Unlike most mitochondrial matrix proteins, it contains a non-cleavable amino-terminal targeting signal. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAA2	NM_006111.3	c.883+847T>C		intron_variant		ENST00000285093.15	NP_006102.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACAA2	ENST00000285093.15	c.883+847T>C		intron_variant		1	NM_006111.3	ENSP00000285093.8
ACAA2	ENST00000587994.5	c.874+847T>C		intron_variant		5		ENSP00000466015.1
ACAA2	ENST00000589432.5	c.718+847T>C		intron_variant		5		ENSP00000466466.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91074 AN: 151886 Hom.: 27427 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.600 AC: 91144 AN: 152004 Hom.: 27444 Cov.: 32 AF XY: 0.599 AC XY: 44530 AN XY: 74290

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.640

Alfa AF: 0.595 Hom.: 3633

Bravo AF: 0.613

Asia WGS AF: 0.592 AC: 2058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.9
DANN	Benign	0.43

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: rs628531; hg19: chr18-47316993;