10-112416935-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_203379.2(ACSL5):c.1131G>A(p.Leu377=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,614,066 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0094 (24 hom., cov: 30)
  • Exomes 𝑓: 0.0010 (32 hom.)
• Consequence: ACSL5 NM_203379.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.31

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 10-112416935-G-A is Benign according to our data. Variant chr10-112416935-G-A is described in ClinVar as [Benign]. Clinvar id is 784211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.31 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00938 (1427/152204) while in subpopulation AFR AF= 0.0326 (1353/41518). AF 95% confidence interval is 0.0311. There are 24 homozygotes in gnomad4. There are 705 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSL5	NM_203379.2	c.1131G>A	p.Leu377=	synonymous_variant	13/21	ENST00000354655.9
ACSL5	NM_016234.4	c.1299G>A	p.Leu433=	synonymous_variant	13/21
ACSL5	NM_001387037.1	c.1299G>A	p.Leu433=	synonymous_variant	13/20
ACSL5	NM_203380.2	c.1131G>A	p.Leu377=	synonymous_variant	13/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSL5	ENST00000354655.9	c.1131G>A	p.Leu377=	synonymous_variant	13/21	2	NM_203379.2	P1
	ENST00000631085.2	n.175+1849C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00937 AC: 1425 AN: 152082 Hom.: 24 Cov.: 30

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00249 AC: 626 AN: 251474 Hom.: 8 AF XY: 0.00197 AC XY: 268 AN XY: 135910

Gnomad AFR exome AF: 0.0338

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000527

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00101 AC: 1478 AN: 1461862 Hom.: 32 Cov.: 30 AF XY: 0.000888 AC XY: 646 AN XY: 727234

Gnomad4 AFR exome AF: 0.0361

Gnomad4 AMR exome AF: 0.00183

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.00240

GnomAD4 genome AF: 0.00938 AC: 1427 AN: 152204 Hom.: 24 Cov.: 30 AF XY: 0.00947 AC XY: 705 AN XY: 74420

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.00379

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00336 Hom.: 5

Bravo AF: 0.0114

Asia WGS AF: 0.00202 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	1.5
Dann	Benign	0.48

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

Other links and lift over

dbSNP: rs11812261; hg19: chr10-114176693;