18-49790623-A-G

Variant names:

• chr18-49790623-A-G
• rs628531
• NM_006111.3:c.883+847T>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+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
• Publications: 5 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=-0.97).
• 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 rank	MANE	Protein	UniProt
ACAA2	NM_006111.3	c.883+847T>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+847T>C		intron_variant	Intron 7 of 9	1	NM_006111.3	ENSP00000285093.8
ACAA2	ENST00000587994.5	c.874+847T>C		intron_variant	Intron 7 of 9	5		ENSP00000466015.1
ACAA2	ENST00000589432.5	c.718+847T>C		intron_variant	Intron 7 of 9	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

African (AFR) AF: 0.603 AC: 24995 AN: 41440

American (AMR) AF: 0.644 AC: 9846 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2406 AN: 3464

East Asian (EAS) AF: 0.548 AC: 2827 AN: 5158

South Asian (SAS) AF: 0.585 AC: 2818 AN: 4816

European-Finnish (FIN) AF: 0.529 AC: 5584 AN: 10548

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.595 AC: 40441 AN: 67980

Other (OTH) AF: 0.640 AC: 1355 AN: 2116

Alfa AF: 0.596 Hom.: 3774

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
PhyloP100		-0.34
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: rs628531; hg19: chr18-47316993;