dbSNP rs77938: ACSL6:c.864+21G>A (chr5-131986801-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.253

Publications

17 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:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACSL6	NM_001009185.3	MANE Select	c.864+21G>A	intron	N/A	NP_001009185.1	Q9UKU0-1
ACSL6	NM_015256.4		c.864+21G>A	intron	N/A	NP_056071.2	Q9UKU0-8
ACSL6	NM_001405475.1		c.858+21G>A	intron	N/A	NP_001392404.1	A0A494C0B6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACSL6	ENST00000651883.2	MANE Select	c.864+21G>A	intron	N/A	ENSP00000499063.2	Q9UKU0-1
ACSL6	ENST00000543479.5	TSL:1	c.834+21G>A	intron	N/A	ENSP00000442124.2	Q9UKU0-6
ACSL6	ENST00000379246.5	TSL:1	c.822+21G>A	intron	N/A	ENSP00000368548.1	Q9UKU0-9

Frequencies

GnomAD3 genomes

AF:

0.620

AC:

94281

AN:

151966

Hom.:

33715

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.773

AC XY:

562001

AN XY:

726964

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

11807

23614

35420

47227

59034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20550

41100

61650

82200

102750

<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:

0.620

AC:

94302

AN:

152086

Hom.:

33718

Cov.:

AF XY:

0.621

AC XY:

46164

AN XY:

74350

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1427

2854

4282

5709

7136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<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:

0.747

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

(source)

DANN

Benign

0.64

PhyloP100

-0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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