18-49783514-G-C

Variant names:

• chr18-49783514-G-C
• rs7233791
• NM_006111.3:c.*333C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006111.3(ACAA2):​c.*333C>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0844 in 188,528 control chromosomes in the GnomAD database, including 861 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 0.088 (750 hom., cov: 33)
  • Exomes 𝑓: 0.069 (111 hom.)
• Consequence: ACAA2 NM_006111.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.03
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006111.3. 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
	ACAA2	NM_006111.3	MANE Select	c.*333C>G		3_prime_UTR	Exon 10 of 10	NP_006102.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAA2	ENST00000285093.15	TSL:1 MANE Select	c.*333C>G		3_prime_UTR	Exon 10 of 10	ENSP00000285093.8
	ACAA2	ENST00000591171.1	TSL:2	n.1841C>G		non_coding_transcript_exon	Exon 2 of 2
	ACAA2	ENST00000587994.5	TSL:5	c.*333C>G		3_prime_UTR	Exon 10 of 10	ENSP00000466015.1

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 13393 AN: 152036 Hom.: 744 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0498

Gnomad ASJ AF: 0.0815

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0415

Gnomad FIN AF: 0.0687

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0832

GnomAD4 exome AF: 0.0689 AC: 2505 AN: 36374 Hom.: 111 Cov.: 0 AF XY: 0.0678 AC XY: 1260 AN XY: 18588

African (AFR) AF: 0.169 AC: 259 AN: 1536

American (AMR) AF: 0.0415 AC: 108 AN: 2604

Ashkenazi Jewish (ASJ) AF: 0.0987 AC: 122 AN: 1236

East Asian (EAS) AF: 0.114 AC: 308 AN: 2702

South Asian (SAS) AF: 0.0482 AC: 67 AN: 1390

European-Finnish (FIN) AF: 0.0725 AC: 116 AN: 1600

Middle Eastern (MID) AF: 0.0707 AC: 13 AN: 184

European-Non Finnish (NFE) AF: 0.0575 AC: 1308 AN: 22748

Other (OTH) AF: 0.0859 AC: 204 AN: 2374

GnomAD4 genome AF: 0.0882 AC: 13413 AN: 152154 Hom.: 750 Cov.: 33 AF XY: 0.0875 AC XY: 6508 AN XY: 74396

African (AFR) AF: 0.166 AC: 6881 AN: 41490

American (AMR) AF: 0.0498 AC: 761 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0815 AC: 283 AN: 3472

East Asian (EAS) AF: 0.135 AC: 697 AN: 5180

South Asian (SAS) AF: 0.0415 AC: 200 AN: 4818

European-Finnish (FIN) AF: 0.0687 AC: 727 AN: 10588

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0531 AC: 3610 AN: 67994

Other (OTH) AF: 0.0823 AC: 174 AN: 2114

Alfa AF: 0.0218 Hom.: 5

Bravo AF: 0.0922

Asia WGS AF: 0.0870 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		4.0
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: rs7233791; hg19: chr18-47309884;