5-131956163-A-G

Variant summary

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

The NM_001009185.3(ACSL6):c.2032-1792T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,066 control chromosomes in the GnomAD database, including 3,840 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 0.22 (3840 hom., cov: 32)
• Consequence: ACSL6 NM_001009185.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSL6	NM_001009185.3	c.2032-1792T>C		intron_variant		ENST00000651883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSL6	ENST00000651883.2	c.2032-1792T>C		intron_variant			NM_001009185.3	A1
	ENST00000446275.1	n.118-3442A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32793 AN: 151948 Hom.: 3834 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.216 AC: 32827 AN: 152066 Hom.: 3840 Cov.: 32 AF XY: 0.222 AC XY: 16497 AN XY: 74314

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.206

Alfa AF: 0.209 Hom.: 679

Bravo AF: 0.214

Asia WGS AF: 0.369 AC: 1283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	13
Dann	Benign	0.82

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: rs615305; hg19: chr5-131291856;