Genetic Variant NM_001271783.2:c.409C>T (chr12-29297064-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001271783.2(FAR2):c.409C>T(p.Leu137Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L137V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FAR2
NM_001271783.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.549

Publications

0 publications found

Variant links:

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]

FAR2 links:

ENSG00000257176 (HGNC:58443):

ENSG00000257176 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05321628).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271783.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAR2	NM_001271783.2	MANE Select	c.409C>T	p.Leu137Phe	missense	Exon 4 of 12	NP_001258712.1	Q96K12-1
FAR2	NM_018099.5		c.409C>T	p.Leu137Phe	missense	Exon 4 of 12	NP_060569.3
FAR2	NM_001271784.2		c.118C>T	p.Leu40Phe	missense	Exon 3 of 11	NP_001258713.1	Q96K12-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAR2	ENST00000536681.8	TSL:1 MANE Select	c.409C>T	p.Leu137Phe	missense	Exon 4 of 12	ENSP00000443291.2	Q96K12-1
FAR2	ENST00000182377.8	TSL:1	c.409C>T	p.Leu137Phe	missense	Exon 4 of 12	ENSP00000182377.4	Q96K12-1
FAR2	ENST00000946761.1		c.409C>T	p.Leu137Phe	missense	Exon 4 of 13	ENSP00000616820.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459894

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726158

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33356

American (AMR)

AF:

0.00

AC:

AN:

44386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.00

AC:

AN:

85818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111214

Other (OTH)

AF:

0.00

AC:

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.060

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.44

M_CAP

Benign

0.0054

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.15

PhyloP100

-0.55

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.2

REVEL

Benign

0.050

Sift

Benign

0.31

Sift4G

Benign

0.73

Polyphen

0.0020

Vest4

0.21

MutPred

0.47

Gain of catalytic residue at L136 (P = 0.0378)

MVP

0.10

MPC

0.48

ClinPred

0.025

GERP RS

-0.28

Varity_R

0.074

gMVP

0.19

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over