rs11195951

Variant names:

• chr10-112406218-A-T
• rs11195951
• NM_203379.2:c.432+1412A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203379.2(ACSL5):​c.432+1412A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,136 control chromosomes in the GnomAD database, including 3,670 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3668 hom., cov: 31)
  • Exomes 𝑓: 0.35 (2 hom.)
• Consequence: ACSL5 NM_203379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 2 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]

ACSL5 Gene-Disease associations (from GenCC):

• diarrhea 13

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000232934 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL5	NM_203379.2	c.432+1412A>T		intron_variant	Intron 5 of 20	ENST00000354655.9	NP_976313.1
ACSL5	NM_016234.4	c.600+1412A>T		intron_variant	Intron 5 of 20		NP_057318.2
ACSL5	NM_001387037.1	c.600+1412A>T		intron_variant	Intron 5 of 19		NP_001373966.1
ACSL5	NM_203380.2	c.432+1412A>T		intron_variant	Intron 5 of 20		NP_976314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL5	ENST00000354655.9	c.432+1412A>T		intron_variant	Intron 5 of 20	2	NM_203379.2	ENSP00000346680.4

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30479 AN: 151998 Hom.: 3668 Cov.: 31

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.350 AC: 7 AN: 20 Hom.: 2 Cov.: 0 AF XY: 0.389 AC XY: 7 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.278 AC: 5 AN: 18

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.200 AC: 30486 AN: 152116 Hom.: 3668 Cov.: 31 AF XY: 0.203 AC XY: 15108 AN XY: 74348

African (AFR) AF: 0.0593 AC: 2462 AN: 41532

American (AMR) AF: 0.198 AC: 3021 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1171 AN: 3470

East Asian (EAS) AF: 0.216 AC: 1119 AN: 5174

South Asian (SAS) AF: 0.230 AC: 1106 AN: 4808

European-Finnish (FIN) AF: 0.314 AC: 3321 AN: 10572

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.258 AC: 17562 AN: 67970

Other (OTH) AF: 0.228 AC: 481 AN: 2112

Alfa AF: 0.227 Hom.: 541

Bravo AF: 0.186

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.85
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs11195951; hg19: chr10-114165976;