rs174616

Variant names:

• chr11-61861650-G-A
• rs174616
• NM_004265.4:c.883-1322G>A

Variant summary

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

The NM_004265.4(FADS2):​c.883-1322G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,124 control chromosomes in the GnomAD database, including 19,862 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 0.50 (19862 hom., cov: 33)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• Publications: 48 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FADS2	NM_004265.4	c.883-1322G>A		intron_variant	Intron 7 of 11	ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.817-1322G>A		intron_variant	Intron 7 of 11		NP_001268430.1
FADS2	NM_001281502.1	c.790-1322G>A		intron_variant	Intron 7 of 11		NP_001268431.1
FADS2	XM_047427889.1	c.883-1322G>A		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.883-1322G>A		intron_variant	Intron 7 of 11	1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76269 AN: 152006 Hom.: 19824 Cov.: 33

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.502 AC: 76370 AN: 152124 Hom.: 19862 Cov.: 33 AF XY: 0.498 AC XY: 37032 AN XY: 74362

African (AFR) AF: 0.586 AC: 24312 AN: 41506

American (AMR) AF: 0.617 AC: 9447 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1709 AN: 3468

East Asian (EAS) AF: 0.256 AC: 1323 AN: 5160

South Asian (SAS) AF: 0.406 AC: 1958 AN: 4826

European-Finnish (FIN) AF: 0.444 AC: 4694 AN: 10582

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.461 AC: 31313 AN: 67966

Other (OTH) AF: 0.517 AC: 1092 AN: 2112

Alfa AF: 0.516 Hom.: 7313

Bravo AF: 0.520

Asia WGS AF: 0.361 AC: 1253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.50
PhyloP100		-0.47
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: rs174616; hg19: chr11-61629122;