rs174556

Positions:

• chr11-61813163-C-T

Variant summary

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

The NM_013402.7(FADS1):​c.486+80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 848,108 control chromosomes in the GnomAD database, including 45,156 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 0.26 (6846 hom., cov: 30)
  • Exomes 𝑓: 0.31 (38310 hom.)
• Consequence: FADS1 NM_013402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520

Genes affected

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]

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FADS1	NM_013402.7	c.486+80G>A		intron_variant		ENST00000350997.12	NP_037534.5
FADS1	XM_011545022.3	c.273+80G>A		intron_variant			XP_011543324.1
FADS1	XM_047426935.1	c.63+80G>A		intron_variant			XP_047282891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS1	ENST00000350997.12	c.486+80G>A		intron_variant		1	NM_013402.7	ENSP00000322229	P1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39514 AN: 151784 Hom.: 6826 Cov.: 30

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.308 AC: 214641 AN: 696206 Hom.: 38310 AF XY: 0.297 AC XY: 111574 AN XY: 375848

Gnomad4 AFR exome AF: 0.0678

Gnomad4 AMR exome AF: 0.627

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.318

GnomAD4 genome AF: 0.260 AC: 39548 AN: 151902 Hom.: 6846 Cov.: 30 AF XY: 0.267 AC XY: 19831 AN XY: 74218

Gnomad4 AFR AF: 0.0709

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.304

Alfa AF: 0.268 Hom.: 3057

Bravo AF: 0.263

Asia WGS AF: 0.357 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs174556; hg19: chr11-61580635; COSMIC: COSV57246628; COSMIC: COSV57246628;