chr5-132000594-T-G

Variant names:

• chr5-132000594-T-G
• rs440970
• NM_001009185.3:c.50-6343A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009185.3. 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.50-6343A>C		intron	N/A	NP_001009185.1
	ACSL6	NM_015256.4		c.50-6343A>C		intron	N/A	NP_056071.2
	ACSL6	NM_001405475.1		c.-26-6343A>C		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.50-6343A>C		intron	N/A	ENSP00000499063.2
	ACSL6	ENST00000379246.5	TSL:1	c.8-6343A>C		intron	N/A	ENSP00000368548.1
	ACSL6	ENST00000434099.6	TSL:1	c.50-6343A>C		intron	N/A	ENSP00000397507.2

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

African (AFR) AF: 0.223 AC: 9238 AN: 41366

American (AMR) AF: 0.408 AC: 6234 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1479 AN: 3468

East Asian (EAS) AF: 0.450 AC: 2318 AN: 5152

South Asian (SAS) AF: 0.658 AC: 3148 AN: 4782

European-Finnish (FIN) AF: 0.491 AC: 5170 AN: 10536

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28943 AN: 67884

Other (OTH) AF: 0.379 AC: 799 AN: 2106

Alfa AF: 0.408 Hom.: 54808

Bravo AF: 0.359

Asia WGS AF: 0.519 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.49
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs440970; hg19: chr5-131336287;