Variant 2-222934572-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The ENST00000357430.8(ACSL3):c.1890G>A(p.Lys630=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00124 in 1,588,138 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 14 hom. )

Consequence

ACSL3
ENST00000357430.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.61

Variant links:

Genes affected

ACSL3 (HGNC:3570): (acyl-CoA synthetase long chain family member 3) The protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family. Although differing in substrate specificity, subcellular localization, and tissue distribution, all isozymes of this family convert free long-chain fatty acids into fatty acyl-CoA esters, and thereby play a key role in lipid biosynthesis and fatty acid degradation. This isozyme is highly expressed in brain, and preferentially utilizes myristate, arachidonate, and eicosapentaenoate as substrates. The amino acid sequence of this isozyme is 92% identical to that of rat homolog. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACSL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 2-222934572-G-A is Benign according to our data. Variant chr2-222934572-G-A is described in ClinVar as [Benign]. Clinvar id is 714170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00656 (999/152256) while in subpopulation AFR AF= 0.0228 (947/41540). AF 95% confidence interval is 0.0216. There are 11 homozygotes in gnomad4. There are 453 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ACSL3	NM_004457.5 linkuse as main transcript	c.1890G>A	p.Lys630=	synonymous_variant	16/17	ENST00000357430.8	NP_004448.2
ACSL3	NM_001354158.2 linkuse as main transcript	c.1890G>A	p.Lys630=	synonymous_variant	15/16		NP_001341087.1
ACSL3	NM_001354159.2 linkuse as main transcript	c.1890G>A	p.Lys630=	synonymous_variant	14/15		NP_001341088.1
ACSL3	NM_203372.3 linkuse as main transcript	c.1890G>A	p.Lys630=	synonymous_variant	15/16		NP_976251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSL3	ENST00000357430.8 linkuse as main transcript	c.1890G>A	p.Lys630=	synonymous_variant	16/17	1	NM_004457.5	ENSP00000350012	P1

Frequencies

GnomAD3 genomes

AF:

0.00653

AC:

993

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00165

AC:

396

AN:

239434

Hom.:

AF XY:

0.00122

AC XY:

158

AN XY:

129444

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.000963

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000362

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.000517

GnomAD4 exome

AF:

0.000676

AC:

970

AN:

1435882

Hom.:

Cov.:

AF XY:

0.000598

AC XY:

425

AN XY:

710742

show subpopulations

Gnomad4 AFR exome

AF:

0.0257

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000378

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000118

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.00656

AC:

999

AN:

152256

Hom.:

Cov.:

AF XY:

0.00608

AC XY:

453

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0228

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00297

Hom.:

Bravo

AF:

0.00701

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

8.4

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

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

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