5-132000594-T-G

Position:

• chr5-132000594-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001009185.3(ACSL6):​c.50-6343A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,766 control chromosomes in the GnomAD database, including 11,889 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 0.38 (11889 hom., cov: 31)
• Consequence: ACSL6 NM_001009185.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.963

Genes affected

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSL6	NM_001009185.3	c.50-6343A>C		intron_variant		ENST00000651883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSL6	ENST00000651883.2	c.50-6343A>C		intron_variant			NM_001009185.3	A1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57675 AN: 151646 Hom.: 11875 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.380 AC: 57722 AN: 151766 Hom.: 11889 Cov.: 31 AF XY: 0.392 AC XY: 29050 AN XY: 74162

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.379

Alfa AF: 0.414 Hom.: 27257

Bravo AF: 0.359

Asia WGS AF: 0.519 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs440970; hg19: chr5-131336287;