rs968567

chr11-61828092-C-T

Variant summary

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

The ENST00000257261.10(FADS2):c.142-9686C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,281,338 control chromosomes in the GnomAD database, including 18,233 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 0.11 (1214 hom., cov: 32)
  • Exomes 𝑓: 0.17 (17019 hom.)
• Consequence: FADS2 ENST00000257261.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336

Genes affected

FADS2 (HGNC:3575): (fatty acid desaturase 2) The protein encoded by this gene is a member of the fatty acid desaturase (FADS) gene family. Desaturase enzymes regulate unsaturation of fatty acids through the introduction of double bonds between defined carbons of the fatty acyl chain. FADS family members are considered fusion products composed of an N-terminal cytochrome b5-like domain and a C-terminal multiple membrane-spanning desaturase portion, both of which are characterized by conserved histidine motifs. This gene is clustered with family members at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

FADS1 (HGNC:3574): (fatty acid desaturase 1) The protein encoded by this gene is a member of the fatty acid desaturase (FADS) gene family. Desaturase enzymes regulate unsaturation of fatty acids through the introduction of double bonds between defined carbons of the fatty acyl chain. FADS family members are considered fusion products composed of an N-terminal cytochrome b5-like domain and a C-terminal multiple membrane-spanning desaturase portion, both of which are characterized by conserved histidine motifs. This gene is clustered with family members FADS1 and FADS2 at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FADS2	XM_047427889.1	c.-299C>T		5_prime_UTR_variant	2/13
FADS2	NM_001281501.1	c.142-9686C>T		intron_variant
FADS2	NM_001281502.1	c.115-9686C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FADS2	ENST00000257261.10	c.142-9686C>T		intron_variant		1
FADS1	ENST00000421879.5	c.-49+1109G>A		intron_variant		3
FADS1	ENST00000448607.1	c.-49+358G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16315 AN: 151724 Hom.: 1215 Cov.: 32

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0838

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.166 AC: 187416 AN: 1129496 Hom.: 17019 Cov.: 30 AF XY: 0.164 AC XY: 88582 AN XY: 540058

Gnomad4 AFR exome AF: 0.0248

Gnomad4 AMR exome AF: 0.0744

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.000576

Gnomad4 SAS exome AF: 0.0640

Gnomad4 FIN exome AF: 0.0992

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.107 AC: 16310 AN: 151842 Hom.: 1214 Cov.: 32 AF XY: 0.101 AC XY: 7530 AN XY: 74202

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.0835

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0560

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.130

Alfa AF: 0.145 Hom.: 765

Bravo AF: 0.104

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	11
Dann	Benign	0.95

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: rs968567; hg19: chr11-61595564;