rs174620

Positions:

• chr11-61862275-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004265.4(FADS2):​c.883-697A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,098 control chromosomes in the GnomAD database, including 15,635 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 (15610 hom., cov: 31)
  • Exomes 𝑓: 0.46 (25 hom.)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FADS2	NM_004265.4	c.883-697A>G		intron_variant		ENST00000278840.9
FADS2	NM_001281501.1	c.817-697A>G		intron_variant
FADS2	NM_001281502.1	c.790-697A>G		intron_variant
FADS2	XM_047427889.1	c.883-697A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FADS2	ENST00000278840.9	c.883-697A>G		intron_variant		1	NM_004265.4	P1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66615 AN: 151776 Hom.: 15581 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.442

GnomAD4 exome AF: 0.460 AC: 93 AN: 202 Hom.: 25 Cov.: 0 AF XY: 0.472 AC XY: 67 AN XY: 142

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.471

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.439 AC: 66691 AN: 151896 Hom.: 15610 Cov.: 31 AF XY: 0.429 AC XY: 31869 AN XY: 74232

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.436

Alfa AF: 0.438 Hom.: 1860

Bravo AF: 0.438

Asia WGS AF: 0.201 AC: 698 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	1.3
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs174620; hg19: chr11-61629747;