Variant 4-184763170-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001995.5(ACSL1):c.1518C>T(p.Gly506Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00849 in 1,613,058 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0086 ( 101 hom. )

Consequence

ACSL1
NM_001995.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.204

Variant links:

Genes affected

ACSL1 (HGNC:3569): (acyl-CoA synthetase long chain family member 1) 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. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ACSL1 links:

ACSL1 (HGNC:):

ACSL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 4-184763170-G-A is Benign according to our data. Variant chr4-184763170-G-A is described in ClinVar as [Benign]. Clinvar id is 773712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.204 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00863 (12601/1460790) while in subpopulation MID AF= 0.0248 (143/5760). AF 95% confidence interval is 0.0215. There are 101 homozygotes in gnomad4_exome. There are 6452 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSL1	NM_001995.5 linkuse as main transcript	c.1518C>T	p.Gly506Gly	synonymous_variant	16/21	ENST00000281455.7	NP_001986.2	P33121-1A8K9T3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSL1	ENST00000281455.7 linkuse as main transcript	c.1518C>T	p.Gly506Gly	synonymous_variant	16/21	1	NM_001995.5	ENSP00000281455.2		P33121-1

Frequencies

GnomAD3 genomes

AF:

0.00718

AC:

1093

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00941

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00782

AC:

1958

AN:

250236

Hom.:

AF XY:

0.00815

AC XY:

1102

AN XY:

135282

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00471

Gnomad ASJ exome

AF:

0.0298

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00745

Gnomad FIN exome

AF:

0.00314

Gnomad NFE exome

AF:

0.00991

Gnomad OTH exome

AF:

0.00883

GnomAD4 exome

AF:

0.00863

AC:

12601

AN:

1460790

Hom.:

101

Cov.:

AF XY:

0.00888

AC XY:

6452

AN XY:

726660

show subpopulations

Gnomad4 AFR exome

AF:

0.00195

Gnomad4 AMR exome

AF:

0.00516

Gnomad4 ASJ exome

AF:

0.0301

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00761

Gnomad4 FIN exome

AF:

0.00316

Gnomad4 NFE exome

AF:

0.00895

Gnomad4 OTH exome

AF:

0.0100

GnomAD4 genome

AF:

0.00718

AC:

1094

AN:

152268

Hom.:

Cov.:

AF XY:

0.00736

AC XY:

548

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00807

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.00941

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00883

Hom.:

Bravo

AF:

0.00740

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0122

EpiControl

AF:

0.0122

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 09, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

3.6

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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