rs174455

Variant names:

• chr11-61888645-G-A
• rs174455
• NM_021727.5:c.213+2524C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-61888645-G-A
• chr11-61888645-G-C

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+2524C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,054 control chromosomes in the GnomAD database, including 20,785 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 0.47 (20785 hom., cov: 32)
• Consequence: FADS3 NM_021727.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 54 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.638 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+2524C>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+2524C>T		intron	N/A	ENSP00000278829.2	Q9Y5Q0
	FADS3	ENST00000969795.1		c.213+2524C>T		intron	N/A	ENSP00000639854.1
	FADS3	ENST00000969794.1		c.213+2524C>T		intron	N/A	ENSP00000639853.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71304 AN: 151936 Hom.: 20790 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.469 AC: 71283 AN: 152054 Hom.: 20785 Cov.: 32 AF XY: 0.470 AC XY: 34964 AN XY: 74316

African (AFR) AF: 0.121 AC: 5036 AN: 41524

American (AMR) AF: 0.392 AC: 5993 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2221 AN: 3468

East Asian (EAS) AF: 0.603 AC: 3113 AN: 5162

South Asian (SAS) AF: 0.572 AC: 2753 AN: 4814

European-Finnish (FIN) AF: 0.637 AC: 6715 AN: 10540

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.643 AC: 43671 AN: 67954

Other (OTH) AF: 0.491 AC: 1036 AN: 2112

Alfa AF: 0.556 Hom.: 44544

Bravo AF: 0.435

Asia WGS AF: 0.506 AC: 1761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.68
PhyloP100		-1.0
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: rs174455; hg19: chr11-61656117;