11-61888710-C-A

Variant names:

• chr11-61888710-C-A
• rs174456
• NM_021727.5:c.213+2459G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021727.5(FADS3):​c.213+2459G>T 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 152,008 control chromosomes in the GnomAD database, including 30,029 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 (30029 hom., cov: 31)
• Consequence: FADS3 NM_021727.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.84
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021727.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS3	NM_021727.5	MANE Select	c.213+2459G>T		intron	N/A	NP_068373.1	Q9Y5Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS3	ENST00000278829.7	TSL:1 MANE Select	c.213+2459G>T		intron	N/A	ENSP00000278829.2	Q9Y5Q0
	FADS3	ENST00000969795.1		c.213+2459G>T		intron	N/A	ENSP00000639854.1
	FADS3	ENST00000969794.1		c.213+2459G>T		intron	N/A	ENSP00000639853.1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90408 AN: 151890 Hom.: 30032 Cov.: 31

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.595 AC: 90403 AN: 152008 Hom.: 30029 Cov.: 31 AF XY: 0.596 AC XY: 44287 AN XY: 74290

African (AFR) AF: 0.295 AC: 12227 AN: 41472

American (AMR) AF: 0.516 AC: 7876 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2634 AN: 3470

East Asian (EAS) AF: 0.689 AC: 3556 AN: 5158

South Asian (SAS) AF: 0.630 AC: 3042 AN: 4828

European-Finnish (FIN) AF: 0.775 AC: 8170 AN: 10540

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50693 AN: 67942

Other (OTH) AF: 0.609 AC: 1288 AN: 2114

Alfa AF: 0.657 Hom.: 14530

Bravo AF: 0.560

Asia WGS AF: 0.610 AC: 2122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0010
DANN	Benign	0.49
PhyloP100		-5.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs174456; hg19: chr11-61656182;