rs2239621

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-38132242-C-A
• chr3-38132242-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001607.4(ACAA1):​c.324-237G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,008 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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>T		intron	N/A	NP_001598.1
	ACAA1	NM_001130410.2		c.324-237G>T		intron	N/A	NP_001123882.1
	ACAA1	NR_024024.2		n.416-237G>T		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>T		intron	N/A	ENSP00000333664.8
	ACAA1	ENST00000301810.11	TSL:1	c.324-237G>T		intron	N/A	ENSP00000301810.7
	ACAA1	ENST00000411549.5	TSL:1	n.324-237G>T		intron	N/A	ENSP00000414021.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 175784 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 92396

African (AFR) AF: 0.00 AC: 0 AN: 6580

American (AMR) AF: 0.00 AC: 0 AN: 9480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5466

East Asian (EAS) AF: 0.00 AC: 0 AN: 11896

South Asian (SAS) AF: 0.00 AC: 0 AN: 19114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 784

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 102876

Other (OTH) AF: 0.00 AC: 0 AN: 10146

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152008 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74240

African (AFR) AF: 0.00 AC: 0 AN: 41350

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 11252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.76
DANN	Benign	0.34
PhyloP100		-0.63
PromoterAI		-0.0015	Neutral

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;