NM_001009185.3:c.864+21G>A

Variant names:

• chr5-131986801-C-T
• rs77938
• NM_001009185.3:c.864+21G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.802 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.864+21G>A		intron	N/A	NP_001009185.1
	ACSL6	NM_015256.4		c.864+21G>A		intron	N/A	NP_056071.2
	ACSL6	NM_001405475.1		c.858+21G>A		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.864+21G>A		intron	N/A	ENSP00000499063.2
	ACSL6	ENST00000543479.5	TSL:1	c.834+21G>A		intron	N/A	ENSP00000442124.2
	ACSL6	ENST00000379246.5	TSL:1	c.822+21G>A		intron	N/A	ENSP00000368548.1

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

GnomAD2 exomes AF: 0.705 AC: 177215 AN: 251312 AF XY: 0.726

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 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

African (AFR) AF: 0.228 AC: 7635 AN: 33454

American (AMR) AF: 0.617 AC: 27569 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 17884 AN: 26136

East Asian (EAS) AF: 0.453 AC: 17963 AN: 39674

South Asian (SAS) AF: 0.780 AC: 67242 AN: 86232

European-Finnish (FIN) AF: 0.765 AC: 40851 AN: 53406

Middle Eastern (MID) AF: 0.707 AC: 4076 AN: 5764

European-Non Finnish (NFE) AF: 0.809 AC: 898953 AN: 1111516

Other (OTH) AF: 0.726 AC: 43848 AN: 60378

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

African (AFR) AF: 0.248 AC: 10300 AN: 41456

American (AMR) AF: 0.670 AC: 10236 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2380 AN: 3470

East Asian (EAS) AF: 0.451 AC: 2331 AN: 5164

South Asian (SAS) AF: 0.762 AC: 3675 AN: 4824

European-Finnish (FIN) AF: 0.764 AC: 8093 AN: 10588

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.808 AC: 54920 AN: 67978

Other (OTH) AF: 0.663 AC: 1401 AN: 2112

Alfa AF: 0.747 Hom.: 75938

Bravo AF: 0.591

Asia WGS AF: 0.565 AC: 1964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.0
DANN	Benign	0.64
PhyloP100		-0.25
Mutation Taster		=100/0	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: rs77938; hg19: chr5-131322494; COSMIC: COSV57304005; COSMIC: COSV57304005;