rs10500796

chr11-13677286-A-G

Variant summary

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

The NM_032228.6(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 NM_032228.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.854

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAR1	NM_032228.6	c.-8+8480A>G		intron_variant		ENST00000354817.8
FAR1	XM_011520400.3	c.-8+8480A>G		intron_variant
FAR1	XM_047427690.1	c.-8+8480A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAR1	ENST00000354817.8	c.-8+8480A>G		intron_variant		1	NM_032228.6	P1
FAR1	ENST00000532701.1	c.-8+8480A>G		intron_variant		2

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

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.164

Alfa AF: 0.194 Hom.: 5883

Bravo AF: 0.187

Asia WGS AF: 0.152 AC: 531 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	0.77
Dann	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs10500796; hg19: chr11-13698833;