Variant 5-131985466-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001009185.3(ACSL6):c.865-8C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,613,168 control chromosomes in the GnomAD database, including 27,887 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 1649 hom., cov: 32)

Exomes 𝑓: 0.18 ( 26238 hom. )

Consequence

ACSL6
NM_001009185.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006290

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.829

Variant links:

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]

ACSL6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-131985466-G-C is Benign according to our data. Variant chr5-131985466-G-C is described in ClinVar as [Benign]. Clinvar id is 3059647.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSL6	NM_001009185.3 linkuse as main transcript	c.865-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000651883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSL6	ENST00000651883.2 linkuse as main transcript	c.865-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001009185.3	A1	Q9UKU0-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19576

AN:

152078

Hom.:

1649

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0381

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.0848

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.0417

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.138

GnomAD3 exomes

AF:

0.130

AC:

32560

AN:

250118

Hom.:

2786

AF XY:

0.130

AC XY:

17514

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.0356

Gnomad AMR exome

AF:

0.0961

Gnomad ASJ exome

AF:

0.0876

Gnomad EAS exome

AF:

0.000436

Gnomad SAS exome

AF:

0.0408

Gnomad FIN exome

AF:

0.144

Gnomad NFE exome

AF:

0.199

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.177

AC:

259217

AN:

1460972

Hom.:

26238

Cov.:

AF XY:

0.174

AC XY:

126103

AN XY:

726750

show subpopulations

Gnomad4 AFR exome

AF:

0.0317

Gnomad4 AMR exome

AF:

0.0994

Gnomad4 ASJ exome

AF:

0.0865

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.0452

Gnomad4 FIN exome

AF:

0.144

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.129

AC:

19571

AN:

152196

Hom.:

1649

Cov.:

AF XY:

0.124

AC XY:

9228

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0380

Gnomad4 AMR

AF:

0.138

Gnomad4 ASJ

AF:

0.0848

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.0413

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.198

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.127

Hom.:

524

Bravo

AF:

0.127

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ACSL6-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

Cadd

Benign

5.9

Dann

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000063

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over