18-49783514-G-C

Position:

• chr18-49783514-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000285093.15(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 ENST00000285093.15 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.03

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAA2	NM_006111.3	c.*333C>G		3_prime_UTR_variant	10/10	ENST00000285093.15	NP_006102.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACAA2	ENST00000285093.15	c.*333C>G		3_prime_UTR_variant	10/10	1	NM_006111.3	ENSP00000285093	P4
ACAA2	ENST00000587994.5	c.*333C>G		3_prime_UTR_variant	10/10	5		ENSP00000466015	A1
ACAA2	ENST00000589432.5	c.*333C>G		3_prime_UTR_variant	10/10	5		ENSP00000466466
ACAA2	ENST00000591171.1	n.1841C>G		non_coding_transcript_exon_variant	2/2	2

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

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.0415

Gnomad4 ASJ exome AF: 0.0987

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.0482

Gnomad4 FIN exome AF: 0.0725

Gnomad4 NFE exome AF: 0.0575

Gnomad4 OTH exome AF: 0.0859

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

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0498

Gnomad4 ASJ AF: 0.0815

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.0415

Gnomad4 FIN AF: 0.0687

Gnomad4 NFE AF: 0.0531

Gnomad4 OTH AF: 0.0823

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.91

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: rs7233791; hg19: chr18-47309884;