5-131986801-C-T

Position:

• chr5-131986801-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.864+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,613,362 control chromosomes in the GnomAD database, including 476,887 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 0.62 (33718 hom., cov: 32)
  • Exomes 𝑓: 0.77 (443169 hom.)
• Consequence: ACSL6 NM_001009185.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSL6	NM_001009185.3	c.864+21G>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.864+21G>A		intron_variant			NM_001009185.3	ENSP00000499063	A1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94281 AN: 151966 Hom.: 33715 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.662

GnomAD3 exomes AF: 0.705 AC: 177215 AN: 251312 Hom.: 65840 AF XY: 0.726 AC XY: 98563 AN XY: 135828

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.607

Gnomad ASJ exome AF: 0.686

Gnomad EAS exome AF: 0.463

Gnomad SAS exome AF: 0.782

Gnomad FIN exome AF: 0.760

Gnomad NFE exome AF: 0.810

Gnomad OTH exome AF: 0.741

GnomAD4 exome AF: 0.771 AC: 1126021 AN: 1461276 Hom.: 443169 Cov.: 45 AF XY: 0.773 AC XY: 562001 AN XY: 726964

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.617

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.453

Gnomad4 SAS exome AF: 0.780

Gnomad4 FIN exome AF: 0.765

Gnomad4 NFE exome AF: 0.809

Gnomad4 OTH exome AF: 0.726

GnomAD4 genome AF: 0.620 AC: 94302 AN: 152086 Hom.: 33718 Cov.: 32 AF XY: 0.621 AC XY: 46164 AN XY: 74350

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.808

Gnomad4 OTH AF: 0.663

Alfa AF: 0.764 Hom.: 62756

Bravo AF: 0.591

Asia WGS AF: 0.565 AC: 1964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.0
DANN	Benign	0.64

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: rs77938; hg19: chr5-131322494; COSMIC: COSV57304005; COSMIC: COSV57304005;