rs2240525

chr5-131980191-G-Achr5-131980191-G-T

Variant summary

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

The NM_001009185.3(ACSL6):c.917-3470C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,994 control chromosomes in the GnomAD database, including 17,237 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 0.43 (17237 hom., cov: 32)
• Consequence: ACSL6 NM_001009185.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSL6	NM_001009185.3	c.917-3470C>T		intron_variant		ENST00000651883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSL6	ENST00000651883.2	c.917-3470C>T		intron_variant			NM_001009185.3	A1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65447 AN: 151876 Hom.: 17236 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.431 AC: 65450 AN: 151994 Hom.: 17237 Cov.: 32 AF XY: 0.432 AC XY: 32119 AN XY: 74312

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.479

Alfa AF: 0.517 Hom.: 11188

Bravo AF: 0.416

Asia WGS AF: 0.400 AC: 1388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.13
Dann	Benign	0.47

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: rs2240525; hg19: chr5-131315884;