rs399714

Positions:

• chr5-131983095-C-T

Variant summary

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

The NM_001009185.3(ACSL6):​c.916+2312G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,126 control chromosomes in the GnomAD database, including 12,698 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 0.37 (12698 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: ACSL6 NM_001009185.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.367

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSL6	NM_001009185.3	c.916+2312G>A		intron_variant		ENST00000651883.2	NP_001009185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSL6	ENST00000651883.2	c.916+2312G>A		intron_variant			NM_001009185.3	ENSP00000499063	A1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56197 AN: 152004 Hom.: 12663 Cov.: 33

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.370 AC: 56286 AN: 152122 Hom.: 12698 Cov.: 33 AF XY: 0.370 AC XY: 27541 AN XY: 74372

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.329

Alfa AF: 0.322 Hom.: 1488

Bravo AF: 0.388

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.4
DANN	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs399714; hg19: chr5-131318788;