rs10500796

Variant names:

• chr11-13677286-A-G
• rs10500796
• NM_032228.6:c.-8+8480A>G

Variant summary

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

The ENST00000354817.8(FAR1):​c.-8+8480A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,146 control chromosomes in the GnomAD database, including 2,936 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 0.19 (2936 hom., cov: 32)
• Consequence: FAR1 ENST00000354817.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.854
• Publications: 5 publications found

Genes affected

FAR1 (HGNC:26222): (fatty acyl-CoA reductase 1) The protein encoded by this gene is required for the reduction of fatty acids to fatty alcohols, a process that is required for the synthesis of monoesters and ether lipids. NADPH is required as a cofactor in this reaction, and 16-18 carbon saturated and unsaturated fatty acids are the preferred substrate. This is a peroxisomal membrane protein, and studies suggest that the N-terminus contains a large catalytic domain located on the outside of the peroxisome, while the C-terminus is exposed to the matrix of the peroxisome. Studies indicate that the regulation of this protein is dependent on plasmalogen levels. Mutations in this gene have been associated with individuals affected by severe intellectual disability, early-onset epilepsy, microcephaly, congenital cataracts, growth retardation, and spasticity (PMID: 25439727). A pseudogene of this gene is located on chromosome 13. [provided by RefSeq, Jan 2015]

FAR1 Gene-Disease associations (from GenCC):

• fatty acyl-CoA reductase 1 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen
• spastic paraparesis-cataracts-speech delay syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• fatty acyl-CoA reductase 1 upregulation

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• hereditary spastic paraplegia 9A

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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 = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000354817.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAR1	NM_032228.6	MANE Select	c.-8+8480A>G		intron	N/A	NP_115604.1
	FAR1	NM_001441242.1		c.-8+8480A>G		intron	N/A	NP_001428171.1
	FAR1	NM_001441243.1		c.-8+8480A>G		intron	N/A	NP_001428172.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAR1	ENST00000354817.8	TSL:1 MANE Select	c.-8+8480A>G		intron	N/A	ENSP00000346874.3
	FAR1	ENST00000714156.1		c.-8+6086A>G		intron	N/A	ENSP00000519445.1
	FAR1	ENST00000714157.1		c.-8+8480A>G		intron	N/A	ENSP00000519446.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29006 AN: 152026 Hom.: 2923 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.166

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.191 AC: 29059 AN: 152146 Hom.: 2936 Cov.: 32 AF XY: 0.191 AC XY: 14192 AN XY: 74384

African (AFR) AF: 0.167 AC: 6929 AN: 41516

American (AMR) AF: 0.200 AC: 3059 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3472

East Asian (EAS) AF: 0.180 AC: 930 AN: 5174

South Asian (SAS) AF: 0.133 AC: 639 AN: 4822

European-Finnish (FIN) AF: 0.246 AC: 2599 AN: 10580

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13918 AN: 67976

Other (OTH) AF: 0.164 AC: 347 AN: 2112

Alfa AF: 0.197 Hom.: 12849

Bravo AF: 0.187

Asia WGS AF: 0.152 AC: 531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.36
PhyloP100		-0.85
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: rs10500796; hg19: chr11-13698833;