Variant 10-112426866-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_203379.2(ACSL5):c.1911+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 1,607,038 control chromosomes in the GnomAD database, including 677,299 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.93 ( 66561 hom., cov: 32)

Exomes 𝑓: 0.92 ( 610738 hom. )

Consequence

ACSL5
NM_203379.2 splice_region, intron

Scores

Splicing: ADA: 0.00004319

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00300

Variant links:

Genes affected

ACSL5 (HGNC:16526): (acyl-CoA synthetase long chain family member 5) 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 uterus and spleen, and in trace amounts in normal brain, but has markedly increased levels in malignant gliomas. This gene functions in mediating fatty acid-induced glioma cell growth. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACSL5 links:

ZDHHC6 (HGNC:19160): (zinc finger DHHC-type palmitoyltransferase 6) Enables palmitoyltransferase activity. Involved in positive regulation of mitochondrial fusion and protein palmitoylation. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSL5	NM_203379.2 linkuse as main transcript	c.1911+7G>A		splice_region_variant, intron_variant		ENST00000354655.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSL5	ENST00000354655.9 linkuse as main transcript	c.1911+7G>A		splice_region_variant, intron_variant		2	NM_203379.2	P1	Q9ULC5-1

Frequencies

GnomAD3 genomes

AF:

0.934

AC:

142085

AN:

152180

Hom.:

66501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.973

Gnomad AMI

AF:

0.842

Gnomad AMR

AF:

0.966

Gnomad ASJ

AF:

0.971

Gnomad EAS

AF:

0.988

Gnomad SAS

AF:

0.974

Gnomad FIN

AF:

0.831

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.910

Gnomad OTH

AF:

0.942

GnomAD3 exomes

AF:

0.931

AC:

234078

AN:

251376

Hom.:

109308

AF XY:

0.932

AC XY:

126612

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.973

Gnomad AMR exome

AF:

0.973

Gnomad ASJ exome

AF:

0.965

Gnomad EAS exome

AF:

0.989

Gnomad SAS exome

AF:

0.977

Gnomad FIN exome

AF:

0.820

Gnomad NFE exome

AF:

0.909

Gnomad OTH exome

AF:

0.932

GnomAD4 exome

AF:

0.915

AC:

1331763

AN:

1454740

Hom.:

610738

Cov.:

AF XY:

0.918

AC XY:

664703

AN XY:

724342

show subpopulations

Gnomad4 AFR exome

AF:

0.976

Gnomad4 AMR exome

AF:

0.972

Gnomad4 ASJ exome

AF:

0.968

Gnomad4 EAS exome

AF:

0.990

Gnomad4 SAS exome

AF:

0.977

Gnomad4 FIN exome

AF:

0.826

Gnomad4 NFE exome

AF:

0.906

Gnomad4 OTH exome

AF:

0.925

GnomAD4 genome

AF:

0.934

AC:

142204

AN:

152298

Hom.:

66561

Cov.:

AF XY:

0.932

AC XY:

69422

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.973

Gnomad4 AMR

AF:

0.966

Gnomad4 ASJ

AF:

0.971

Gnomad4 EAS

AF:

0.988

Gnomad4 SAS

AF:

0.974

Gnomad4 FIN

AF:

0.831

Gnomad4 NFE

AF:

0.910

Gnomad4 OTH

AF:

0.943

Alfa

AF:

0.923

Hom.:

48333

Bravo

AF:

0.946

Asia WGS

AF:

0.978

AC:

3402

AN:

3478

EpiCase

AF:

0.920

EpiControl

AF:

0.923

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.92

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000043

dbscSNV1_RF

Benign

0.0

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over