12-29311020-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001271783.2(FAR2):c.769-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0064 in 1,600,528 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (54 hom.)
• Consequence: FAR2 NM_001271783.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00006911
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.241

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 12-29311020-C-T is Benign according to our data. Variant chr12-29311020-C-T is described in ClinVar as [Benign]. Clinvar id is 791498.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAR2	NM_001271783.2	c.769-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000536681.8
LOC100506606	NR_103860.1	n.142-1117G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAR2	ENST00000536681.8	c.769-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001271783.2	P1
	ENST00000553105.1	n.142-1117G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00686 AC: 1043 AN: 152114 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00865

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00639 AC: 1604 AN: 251058 Hom.: 16 AF XY: 0.00646 AC XY: 876 AN XY: 135698

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.0278

Gnomad NFE exome AF: 0.00798

Gnomad OTH exome AF: 0.00490

GnomAD4 exome AF: 0.00635 AC: 9202 AN: 1448296 Hom.: 54 Cov.: 27 AF XY: 0.00626 AC XY: 4517 AN XY: 721542

Gnomad4 AFR exome AF: 0.000783

Gnomad4 AMR exome AF: 0.00117

Gnomad4 ASJ exome AF: 0.00173

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000233

Gnomad4 FIN exome AF: 0.0265

Gnomad4 NFE exome AF: 0.00664

Gnomad4 OTH exome AF: 0.00560

GnomAD4 genome AF: 0.00685 AC: 1043 AN: 152232 Hom.: 9 Cov.: 32 AF XY: 0.00797 AC XY: 593 AN XY: 74418

Gnomad4 AFR AF: 0.000939

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.0332

Gnomad4 NFE AF: 0.00865

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00700 Hom.: 2

Bravo AF: 0.00394

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00589

EpiControl AF: 0.00545

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 24, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	8.6
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000069
dbscSNV1_RF	Benign	0.0
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: rs181186551; hg19: chr12-29463953;