5-131980191-G-A

Variant names:

• chr5-131980191-G-A
• rs2240525
• NM_001009185.3:c.917-3470C>T

Variant summary

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

The ENST00000651883.2(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 ENST00000651883.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 9 publications found

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]

ENSG00000281938 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000651883.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL6	NM_001009185.3	MANE Select	c.917-3470C>T		intron	N/A	NP_001009185.1
	ACSL6	NM_015256.4		c.917-3470C>T		intron	N/A	NP_056071.2
	ACSL6	NM_001405475.1		c.911-3470C>T		intron	N/A	NP_001392404.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL6	ENST00000651883.2	MANE Select	c.917-3470C>T		intron	N/A	ENSP00000499063.2
	ACSL6	ENST00000543479.5	TSL:1	c.887-3470C>T		intron	N/A	ENSP00000442124.2
	ACSL6	ENST00000379246.5	TSL:1	c.875-3470C>T		intron	N/A	ENSP00000368548.1

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

African (AFR) AF: 0.111 AC: 4624 AN: 41478

American (AMR) AF: 0.520 AC: 7948 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1770 AN: 3468

East Asian (EAS) AF: 0.386 AC: 1992 AN: 5166

South Asian (SAS) AF: 0.503 AC: 2419 AN: 4808

European-Finnish (FIN) AF: 0.520 AC: 5486 AN: 10554

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39506 AN: 67944

Other (OTH) AF: 0.479 AC: 1008 AN: 2104

Alfa AF: 0.519 Hom.: 12322

Bravo AF: 0.416

Asia WGS AF: 0.400 AC: 1388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.13
DANN	Benign	0.47
PhyloP100		-1.3
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2240525; hg19: chr5-131315884;