11-61874070-G-T

Variant summary

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

The NM_021727.5(FADS3):c.1287-205C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,088 control chromosomes in the GnomAD database, including 16,279 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 0.44 (16279 hom., cov: 34)
• Consequence: FADS3 NM_021727.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.711

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FADS3	NM_021727.5	c.1287-205C>A		intron_variant		ENST00000278829.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FADS3	ENST00000278829.7	c.1287-205C>A		intron_variant		1	NM_021727.5	P1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67240 AN: 151970 Hom.: 16289 Cov.: 34

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.442 AC: 67228 AN: 152088 Hom.: 16279 Cov.: 34 AF XY: 0.445 AC XY: 33084 AN XY: 74328

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.443

Alfa AF: 0.509 Hom.: 26435

Bravo AF: 0.418

Asia WGS AF: 0.524 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.2
Dann	Benign	0.67

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: rs174450; hg19: chr11-61641542;