dbSNP rs399714: ACSL6:c.916+2312G>A (chr5-131983095-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.916+2312G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,126 control chromosomes in the GnomAD database, including 12,698 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 0.37 ( 12698 hom., cov: 33)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

ACSL6
NM_001009185.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.367

Publications

1 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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL6	NM_001009185.3 link	c.916+2312G>A		intron_variant	Intron 9 of 20	ENST00000651883.2	NP_001009185.1	Q9UKU0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL6	ENST00000651883.2 link	c.916+2312G>A		intron_variant	Intron 9 of 20		NM_001009185.3	ENSP00000499063.2		Q9UKU0-1
ENSG00000281938	ENST00000652469.1 link	n.916+2312G>A		intron_variant	Intron 9 of 25			ENSP00000498837.1		A0A494C116

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56197

AN:

152004

Hom.:

12663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.636

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.515

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.330

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.370

AC:

56286

AN:

152122

Hom.:

12698

Cov.:

AF XY:

0.370

AC XY:

27541

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.637

AC:

26403

AN:

41468

American (AMR)

AF:

0.323

AC:

4941

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

1219

AN:

3470

East Asian (EAS)

AF:

0.515

AC:

2662

AN:

5164

South Asian (SAS)

AF:

0.278

AC:

1340

AN:

4826

European-Finnish (FIN)

AF:

0.292

AC:

3089

AN:

10578

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.229

AC:

15596

AN:

67994

Other (OTH)

AF:

0.329

AC:

696

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1626

3252

4878

6504

8130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.331

Hom.:

1638

Bravo

AF:

0.388

Asia WGS

AF:

0.416

AC:

1447

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

3.4

(source)

DANN

Benign

0.30

PhyloP100

0.37

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over