rs174611

Variant names:

• chr11-61860409-T-C
• rs174611
• NM_004265.4:c.883-2563T>C

Variant summary

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

The NM_004265.4(FADS2):​c.883-2563T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,236 control chromosomes in the GnomAD database, including 4,049 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 0.21 (4049 hom., cov: 33)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 38 publications found

Genes affected

FADS2 (HGNC:3575): (fatty acid desaturase 2) 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 at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

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 (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FADS2	NM_004265.4	c.883-2563T>C		intron_variant	Intron 7 of 11	ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.817-2563T>C		intron_variant	Intron 7 of 11		NP_001268430.1
FADS2	NM_001281502.1	c.790-2563T>C		intron_variant	Intron 7 of 11		NP_001268431.1
FADS2	XM_047427889.1	c.883-2563T>C		intron_variant	Intron 8 of 12		XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.883-2563T>C		intron_variant	Intron 7 of 11	1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31323 AN: 152120 Hom.: 4054 Cov.: 33

Gnomad AFR AF: 0.0748

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.206 AC: 31314 AN: 152236 Hom.: 4049 Cov.: 33 AF XY: 0.200 AC XY: 14919 AN XY: 74426

African (AFR) AF: 0.0746 AC: 3103 AN: 41572

American (AMR) AF: 0.208 AC: 3186 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3470

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5182

South Asian (SAS) AF: 0.127 AC: 614 AN: 4830

European-Finnish (FIN) AF: 0.246 AC: 2603 AN: 10584

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19937 AN: 67990

Other (OTH) AF: 0.225 AC: 476 AN: 2116

Alfa AF: 0.260 Hom.: 10006

Bravo AF: 0.196

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.59
PhyloP100		-0.10
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: rs174611; hg19: chr11-61627881;