rs99780

Positions:

• chr11-61829161-C-T

Variant summary

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

The NM_004265.4(FADS2):​c.207+564C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 153,086 control chromosomes in the GnomAD database, including 11,800 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 0.38 (11753 hom., cov: 32)
  • Exomes 𝑓: 0.27 (47 hom.)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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]

FADS1 (HGNC:3574): (fatty acid desaturase 1) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FADS2	NM_004265.4	c.207+564C>T		intron_variant		ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.142-8617C>T		intron_variant			NP_001268430.1
FADS2	NM_001281502.1	c.115-8617C>T		intron_variant			NP_001268431.1
FADS2	XM_047427889.1	c.207+564C>T		intron_variant			XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.207+564C>T		intron_variant		1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58036 AN: 151970 Hom.: 11711 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.402

GnomAD4 exome AF: 0.274 AC: 273 AN: 998 Hom.: 47 Cov.: 0 AF XY: 0.264 AC XY: 139 AN XY: 526

Gnomad4 AFR exome AF: 0.375

Gnomad4 AMR exome AF: 0.400

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.0926

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.382 AC: 58128 AN: 152088 Hom.: 11753 Cov.: 32 AF XY: 0.385 AC XY: 28613 AN XY: 74344

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.405

Alfa AF: 0.369 Hom.: 1364

Bravo AF: 0.396

Asia WGS AF: 0.398 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.89

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: rs99780; hg19: chr11-61596633;