chr18-49790793-T-G

Variant names:

• chr18-49790793-T-G
• rs627697
• NM_006111.3:c.883+677A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006111.3(ACAA2):​c.883+677A>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 151,976 control chromosomes in the GnomAD database, including 27,435 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 (27435 hom., cov: 32)
• Consequence: ACAA2 NM_006111.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• 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 rank	MANE	Protein	UniProt
ACAA2	NM_006111.3	c.883+677A>C		intron_variant	Intron 7 of 9	ENST00000285093.15	NP_006102.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAA2	ENST00000285093.15	c.883+677A>C		intron_variant	Intron 7 of 9	1	NM_006111.3	ENSP00000285093.8
ACAA2	ENST00000587994.5	c.874+677A>C		intron_variant	Intron 7 of 9	5		ENSP00000466015.1
ACAA2	ENST00000589432.5	c.718+677A>C		intron_variant	Intron 7 of 9	5		ENSP00000466466.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91061 AN: 151860 Hom.: 27419 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.747

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: 91130 AN: 151976 Hom.: 27435 Cov.: 32 AF XY: 0.599 AC XY: 44519 AN XY: 74290

African (AFR) AF: 0.604 AC: 25019 AN: 41432

American (AMR) AF: 0.644 AC: 9845 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2396 AN: 3468

East Asian (EAS) AF: 0.550 AC: 2843 AN: 5172

South Asian (SAS) AF: 0.585 AC: 2816 AN: 4814

European-Finnish (FIN) AF: 0.529 AC: 5582 AN: 10560

Middle Eastern (MID) AF: 0.764 AC: 223 AN: 292

European-Non Finnish (NFE) AF: 0.595 AC: 40403 AN: 67932

Other (OTH) AF: 0.640 AC: 1351 AN: 2112

Alfa AF: 0.601 Hom.: 6473

Bravo AF: 0.613

Asia WGS AF: 0.591 AC: 2056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.82
DANN	Benign	0.58
PhyloP100		-0.16
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: rs627697; hg19: chr18-47317163;