NM_203379.2:c.1911+7G>A

Variant names:

• chr10-112426866-G-A
• rs2256368
• NM_203379.2:c.1911+7G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ACSL5	NM_203379.2	c.1911+7G>A		splice_region_variant, intron_variant	Intron 20 of 20	ENST00000354655.9	NP_976313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL5	ENST00000354655.9	c.1911+7G>A		splice_region_variant, intron_variant	Intron 20 of 20	2	NM_203379.2	ENSP00000346680.4

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

GnomAD2 exomes AF: 0.931 AC: 234078 AN: 251376 AF XY: 0.932

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 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

African (AFR) AF: 0.976 AC: 32522 AN: 33330

American (AMR) AF: 0.972 AC: 43440 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 25262 AN: 26094

East Asian (EAS) AF: 0.990 AC: 39244 AN: 39638

South Asian (SAS) AF: 0.977 AC: 84140 AN: 86098

European-Finnish (FIN) AF: 0.826 AC: 44070 AN: 53358

Middle Eastern (MID) AF: 0.988 AC: 5688 AN: 5760

European-Non Finnish (NFE) AF: 0.906 AC: 1001735 AN: 1105594

Other (OTH) AF: 0.925 AC: 55662 AN: 60158

GnomAD4 genome AF: 0.934 AC: 142204 AN: 152298 Hom.: 66561 Cov.: 32 AF XY: 0.932 AC XY: 69422 AN XY: 74466

African (AFR) AF: 0.973 AC: 40425 AN: 41562

American (AMR) AF: 0.966 AC: 14790 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 3373 AN: 3472

East Asian (EAS) AF: 0.988 AC: 5111 AN: 5174

South Asian (SAS) AF: 0.974 AC: 4705 AN: 4830

European-Finnish (FIN) AF: 0.831 AC: 8809 AN: 10598

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61940 AN: 68032

Other (OTH) AF: 0.943 AC: 1993 AN: 2114

Alfa AF: 0.923 Hom.: 60632

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
PhyloP100		-0.0030
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2256368; hg19: chr10-114186624;