chr11-61889638-C-T

Variant names:

• chr11-61889638-C-T
• rs174460
• NM_021727.5:c.213+1531G>A

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+1531G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,522 control chromosomes in the GnomAD database, including 25,627 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 0.55 (25627 hom., cov: 29)
• Consequence: FADS3 NM_021727.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 16 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 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+1531G>A		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+1531G>A		intron	N/A	ENSP00000278829.2	Q9Y5Q0
	FADS3	ENST00000969795.1		c.213+1531G>A		intron	N/A	ENSP00000639854.1
	FADS3	ENST00000969794.1		c.213+1531G>A		intron	N/A	ENSP00000639853.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82742 AN: 151404 Hom.: 25629 Cov.: 29

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.546 AC: 82732 AN: 151522 Hom.: 25627 Cov.: 29 AF XY: 0.548 AC XY: 40513 AN XY: 73990

African (AFR) AF: 0.255 AC: 10559 AN: 41354

American (AMR) AF: 0.437 AC: 6649 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2476 AN: 3462

East Asian (EAS) AF: 0.679 AC: 3444 AN: 5072

South Asian (SAS) AF: 0.601 AC: 2886 AN: 4800

European-Finnish (FIN) AF: 0.719 AC: 7541 AN: 10484

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47146 AN: 67842

Other (OTH) AF: 0.563 AC: 1186 AN: 2106

Alfa AF: 0.555 Hom.: 12150

Bravo AF: 0.512

Asia WGS AF: 0.597 AC: 2076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.1
DANN	Benign	0.42
PhyloP100		0.30
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: rs174460; hg19: chr11-61657110;