NM_001607.4:c.324-237G>A

Variant names:

• chr3-38132242-C-T
• rs2239621
• NM_001607.4:c.324-237G>A

Variant summary

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

The NM_001607.4(ACAA1):​c.324-237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 327,298 control chromosomes in the GnomAD database, including 18,356 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 0.35 (10686 hom., cov: 32)
  • Exomes 𝑓: 0.29 (7670 hom.)
• Consequence: ACAA1 NM_001607.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• Publications: 19 publications found

Genes affected

ACAA1 (HGNC:82): (acetyl-CoA acyltransferase 1) This gene encodes an enzyme operative in the beta-oxidation system of the peroxisomes. Deficiency of this enzyme leads to pseudo-Zellweger syndrome. Alternative splicing results in multiple transcript variants. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001607.4. 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
	ACAA1	NM_001607.4	MANE Select	c.324-237G>A		intron	N/A	NP_001598.1
	ACAA1	NM_001130410.2		c.324-237G>A		intron	N/A	NP_001123882.1
	ACAA1	NR_024024.2		n.416-237G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAA1	ENST00000333167.13	TSL:1 MANE Select	c.324-237G>A		intron	N/A	ENSP00000333664.8
	ACAA1	ENST00000301810.11	TSL:1	c.324-237G>A		intron	N/A	ENSP00000301810.7
	ACAA1	ENST00000411549.5	TSL:1	n.324-237G>A		intron	N/A	ENSP00000414021.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53559 AN: 151954 Hom.: 10646 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.294 AC: 51583 AN: 175226 Hom.: 7670 Cov.: 2 AF XY: 0.291 AC XY: 26841 AN XY: 92118

African (AFR) AF: 0.562 AC: 3679 AN: 6548

American (AMR) AF: 0.286 AC: 2705 AN: 9448

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 1523 AN: 5450

East Asian (EAS) AF: 0.343 AC: 4068 AN: 11858

South Asian (SAS) AF: 0.258 AC: 4923 AN: 19048

European-Finnish (FIN) AF: 0.269 AC: 2532 AN: 9418

Middle Eastern (MID) AF: 0.381 AC: 297 AN: 780

European-Non Finnish (NFE) AF: 0.281 AC: 28844 AN: 102570

Other (OTH) AF: 0.298 AC: 3012 AN: 10106

GnomAD4 genome AF: 0.353 AC: 53659 AN: 152072 Hom.: 10686 Cov.: 32 AF XY: 0.351 AC XY: 26118 AN XY: 74334

African (AFR) AF: 0.562 AC: 23293 AN: 41440

American (AMR) AF: 0.285 AC: 4352 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3470

East Asian (EAS) AF: 0.331 AC: 1705 AN: 5156

South Asian (SAS) AF: 0.232 AC: 1121 AN: 4834

European-Finnish (FIN) AF: 0.268 AC: 2836 AN: 10586

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18378 AN: 67976

Other (OTH) AF: 0.348 AC: 735 AN: 2114

Alfa AF: 0.287 Hom.: 11252

Bravo AF: 0.367

Asia WGS AF: 0.295 AC: 1025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.98
DANN	Benign	0.18
PhyloP100		-0.63
PromoterAI		-0.0032	Neutral
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: rs2239621; hg19: chr3-38173733;