rs2256368

Positions:

• chr10-112426866-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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

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]

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]

ACMG classification

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	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	c.1911+7G>A		splice_region_variant, intron_variant		2	NM_203379.2	P1

Frequencies

GnomAD3 genomes AF: 0.934 AC: 142085 AN: 152180 Hom.: 66501 Cov.: 32

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

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.: 32 AF XY: 0.918 AC XY: 664703 AN XY: 724342

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.: 32 AF XY: 0.932 AC XY: 69422 AN XY: 74466

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

Other links and lift over

dbSNP: rs2256368; hg19: chr10-114186624;