rs1000778

Positions:

• chr11-61887833-A-G
• chr11-61887833-A-T

Variant summary

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

The NM_021727.5(FADS3):​c.213+3336T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,124 control chromosomes in the GnomAD database, including 30,179 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 0.60 (30179 hom., cov: 33)
• Consequence: FADS3 NM_021727.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

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]

FADS3 (HGNC:):

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	Protein	UniProt
FADS3	NM_021727.5	c.213+3336T>C		intron_variant		ENST00000278829.7	NP_068373.1
FADS3	XM_017017723.1	c.351+4026T>C		intron_variant			XP_016873212.1
FADS3	XM_017017724.1	c.351+4026T>C		intron_variant			XP_016873213.1
FADS3	XM_011545023.2	c.213+3336T>C		intron_variant			XP_011543325.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS3	ENST00000278829.7	c.213+3336T>C		intron_variant		1	NM_021727.5	ENSP00000278829.2
FADS3	ENST00000525588.5	c.213+3336T>C		intron_variant		5		ENSP00000432206.1
FADS3	ENST00000527697.5	c.-160+4026T>C		intron_variant		5		ENSP00000431533.1
FADS3	ENST00000414624.6	n.286+3336T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90845 AN: 152006 Hom.: 30181 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.597 AC: 90839 AN: 152124 Hom.: 30179 Cov.: 33 AF XY: 0.599 AC XY: 44509 AN XY: 74348

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.612

Alfa AF: 0.711 Hom.: 69230

Bravo AF: 0.563

Asia WGS AF: 0.611 AC: 2125 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	1.1
DANN	Benign	0.72

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: rs1000778; hg19: chr11-61655305;