rs958478

Positions:

• chr12-29202791-C-A
• chr12-29202791-C-G
• chr12-29202791-C-T

Variant summary

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

The ENST00000536681.8(FAR2):​c.-39+53384C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,044 control chromosomes in the GnomAD database, including 43,445 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 0.74 (43445 hom., cov: 32)
• Consequence: FAR2 ENST00000536681.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928

Genes affected

FAR2 (HGNC:25531): (fatty acyl-CoA reductase 2) This gene belongs to the short chain dehydrogenase/reductase superfamily. It encodes a reductase enzyme involved in the first step of wax biosynthesis wherein fatty acids are converted to fatty alcohols. The encoded peroxisomal protein utilizes saturated fatty acids of 16 or 18 carbons as preferred substrates. Alternatively spliced transcript variants have been observed for this gene. Related pseudogenes have been identified on chromosomes 2, 14 and 22. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAR2	NM_001271783.2	c.-39+53384C>A		intron_variant		ENST00000536681.8	NP_001258712.1
FAR2	XM_011520747.3	c.-6374C>A		5_prime_UTR_variant	1/12		XP_011519049.1
FAR2	XM_011520748.4	c.-6374C>A		5_prime_UTR_variant	1/12		XP_011519050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAR2	ENST00000536681.8	c.-39+53384C>A		intron_variant		1	NM_001271783.2	ENSP00000443291	P1

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112053 AN: 151926 Hom.: 43420 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.721

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

GnomAD4 genome AF: 0.737 AC: 112125 AN: 152044 Hom.: 43445 Cov.: 32 AF XY: 0.737 AC XY: 54814 AN XY: 74330

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.817

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.906

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.721

Alfa AF: 0.784 Hom.: 5995

Bravo AF: 0.729

Asia WGS AF: 0.740 AC: 2570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.76

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: rs958478; hg19: chr12-29355724;