rs174464

chr11-61890454-A-G

Variant summary

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

The NM_021727.5(FADS3):c.213+715T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,280 control chromosomes in the GnomAD database, including 30,060 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 0.59 (29994 hom., cov: 32)
  • Exomes 𝑓: 0.73 (66 hom.)
• Consequence: FADS3 NM_021727.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412

Genes affected

FADS3 (HGNC:3576): (fatty acid desaturase 3) 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FADS3	NM_021727.5	c.213+715T>C		intron_variant		ENST00000278829.7
FADS3	XM_011545023.2	c.213+715T>C		intron_variant
FADS3	XM_017017723.1	c.351+1405T>C		intron_variant
FADS3	XM_017017724.1	c.351+1405T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FADS3	ENST00000278829.7	c.213+715T>C		intron_variant		1	NM_021727.5	P1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90374 AN: 151928 Hom.: 29996 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.610

GnomAD4 exome AF: 0.726 AC: 170 AN: 234 Hom.: 66 AF XY: 0.726 AC XY: 138 AN XY: 190

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.591

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.759

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.594 AC: 90370 AN: 152046 Hom.: 29994 Cov.: 32 AF XY: 0.596 AC XY: 44296 AN XY: 74334

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.760

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.608

Alfa AF: 0.647 Hom.: 5030

Bravo AF: 0.560

Asia WGS AF: 0.608 AC: 2115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.0
Dann	Benign	0.54

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: rs174464; hg19: chr11-61657926;