5-131974979-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001009185.3(ACSL6):c.991-9C>G variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.000948 in 1,613,306 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00080 (8 hom.)
• Consequence: ACSL6 NM_001009185.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.9907
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.46

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 5-131974979-G-C is Benign according to our data. Variant chr5-131974979-G-C is described in ClinVar as [Benign]. Clinvar id is 716862.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSL6	NM_001009185.3	c.991-9C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000651883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSL6	ENST00000651883.2	c.991-9C>G		splice_polypyrimidine_tract_variant, intron_variant			NM_001009185.3	A1

Frequencies

GnomAD3 genomes AF: 0.00234 AC: 356 AN: 152142 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00102 AC: 254 AN: 249780 Hom.: 2 AF XY: 0.000859 AC XY: 116 AN XY: 134986

Gnomad AFR exome AF: 0.00429

Gnomad AMR exome AF: 0.00215

Gnomad ASJ exome AF: 0.000997

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000726

Gnomad OTH exome AF: 0.00312

GnomAD4 exome AF: 0.000804 AC: 1174 AN: 1461046 Hom.: 8 Cov.: 31 AF XY: 0.000764 AC XY: 555 AN XY: 726734

Gnomad4 AFR exome AF: 0.00439

Gnomad4 AMR exome AF: 0.00265

Gnomad4 ASJ exome AF: 0.000881

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000614

Gnomad4 OTH exome AF: 0.00257

GnomAD4 genome AF: 0.00233 AC: 355 AN: 152260 Hom.: 3 Cov.: 32 AF XY: 0.00206 AC XY: 153 AN XY: 74442

Gnomad4 AFR AF: 0.00431

Gnomad4 AMR AF: 0.00680

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000750

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.000805 Hom.: 0

Bravo AF: 0.00362

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
Cadd	Benign	22
Dann	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.90
SpliceAI score (max)		0.010		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: rs150654858; hg19: chr5-131310672;