5-132012478-A-G

Variant names:

• chr5-132012478-A-G
• rs246999
• ENST00000432558.1:n.99-211A>G

Variant summary

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

The ENST00000432558.1(ENSG00000231585):​n.99-211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,152 control chromosomes in the GnomAD database, including 47,058 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 0.78 (47058 hom., cov: 32)
• Consequence: ENSG00000231585 ENST00000432558.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.644
• Publications: 3 publications found

Genes affected

ENSG00000231585 (HGNC:):

ACSL6 (HGNC:16496): (acyl-CoA synthetase long chain family member 6) The protein encoded by this gene catalyzes the formation of acyl-CoA from fatty acids, ATP, and CoA, using magnesium as a cofactor. The encoded protein plays a major role in fatty acid metabolism in the brain. Translocations with the ETV6 gene are causes of myelodysplastic syndrome with basophilia, acute myelogenous leukemia with eosinophilia, and acute eosinophilic leukemia. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124901062	XR_007058933.1	n.90+933A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000231585	ENST00000432558.1	n.99-211A>G		intron_variant	Intron 1 of 2	3
ENSG00000231585	ENST00000837201.1	n.336+933A>G		intron_variant	Intron 2 of 2
ENSG00000231585	ENST00000837202.1	n.458+933A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118949 AN: 152032 Hom.: 47045 Cov.: 32

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.788

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.782 AC: 119010 AN: 152152 Hom.: 47058 Cov.: 32 AF XY: 0.778 AC XY: 57842 AN XY: 74380

African (AFR) AF: 0.742 AC: 30776 AN: 41492

American (AMR) AF: 0.735 AC: 11249 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2588 AN: 3472

East Asian (EAS) AF: 0.443 AC: 2283 AN: 5156

South Asian (SAS) AF: 0.782 AC: 3767 AN: 4816

European-Finnish (FIN) AF: 0.797 AC: 8441 AN: 10590

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.842 AC: 57234 AN: 68012

Other (OTH) AF: 0.788 AC: 1664 AN: 2112

Alfa AF: 0.809 Hom.: 10367

Bravo AF: 0.771

Asia WGS AF: 0.601 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.5
DANN	Benign	0.80
PhyloP100		0.64
PromoterAI		-0.023	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs246999; hg19: chr5-131348171;