Genetic Variant ACSL6:c.991-9C>G (chr5-131974979-G-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PP3BP6_ModerateBS2

The NM_001009185.3(ACSL6):c.991-9C>G variant causes a 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 intron

Scores

Splicing: ADA: 0.9907

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.46

Publications

0 publications found

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:

ENSG00000281938 (HGNC:):

ENSG00000281938 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

BP6

Variant 5-131974979-G-C is Benign according to our data. Variant chr5-131974979-G-C is described in ClinVar as Benign. ClinVar VariationId is 716862.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACSL6	NM_001009185.3	MANE Select	c.991-9C>G	intron	N/A	NP_001009185.1	Q9UKU0-1
ACSL6	NM_015256.4		c.991-144C>G	intron	N/A	NP_056071.2	Q9UKU0-8
ACSL6	NM_001405475.1		c.985-144C>G	intron	N/A	NP_001392404.1	A0A494C0B6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACSL6	ENST00000651883.2	MANE Select	c.991-9C>G	intron	N/A	ENSP00000499063.2	Q9UKU0-1
ACSL6	ENST00000543479.5	TSL:1	c.961-9C>G	intron	N/A	ENSP00000442124.2	Q9UKU0-6
ACSL6	ENST00000379246.5	TSL:1	c.949-9C>G	intron	N/A	ENSP00000368548.1	Q9UKU0-9

Frequencies

GnomAD3 genomes

AF:

0.00234

AC:

356

AN:

152142

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00102

AC:

254

AN:

249780

AF XY:

0.000859

show subpopulations

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 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.:

Cov.:

AF XY:

0.000764

AC XY:

555

AN XY:

726734

show subpopulations

African (AFR)

AF:

0.00439

AC:

147

AN:

33462

American (AMR)

AF:

0.00265

AC:

118

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.000881

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86048

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00815

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000614

AC:

682

AN:

1111626

Other (OTH)

AF:

0.00257

AC:

155

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

114

170

227

284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00233

AC:

355

AN:

152260

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

153

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00431

AC:

179

AN:

41540

American (AMR)

AF:

0.00680

AC:

104

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000750

AC:

AN:

68028

Other (OTH)

AF:

0.00710

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000805

Hom.:

Bravo

AF:

0.00362

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over