11-61874070-G-T

Variant names:

• chr11-61874070-G-T
• rs174450
• NM_021727.5:c.1287-205C>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.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
• Publications: 34 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 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.1287-205C>A		intron	N/A	NP_068373.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS3	ENST00000278829.7	TSL:1 MANE Select	c.1287-205C>A		intron	N/A	ENSP00000278829.2
	FADS3	ENST00000969795.1		c.1359-205C>A		intron	N/A	ENSP00000639854.1
	FADS3	ENST00000969794.1		c.1335-205C>A		intron	N/A	ENSP00000639853.1

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

African (AFR) AF: 0.254 AC: 10530 AN: 41492

American (AMR) AF: 0.352 AC: 5385 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1729 AN: 3472

East Asian (EAS) AF: 0.611 AC: 3144 AN: 5146

South Asian (SAS) AF: 0.549 AC: 2650 AN: 4824

European-Finnish (FIN) AF: 0.550 AC: 5824 AN: 10582

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.535 AC: 36394 AN: 67968

Other (OTH) AF: 0.443 AC: 933 AN: 2106

Alfa AF: 0.502 Hom.: 56194

Bravo AF: 0.418

Asia WGS AF: 0.524 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.67
PhyloP100		0.71
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: rs174450; hg19: chr11-61641542;