rs174556

Variant names:

• chr11-61813163-C-T
• rs174556
• NM_013402.7:c.486+80G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 182 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FADS1	NM_013402.7	c.486+80G>A		intron_variant	Intron 2 of 11	ENST00000350997.12	NP_037534.5
FADS1	XM_011545022.3	c.273+80G>A		intron_variant	Intron 2 of 11		XP_011543324.1
FADS1	XM_047426935.1	c.63+80G>A		intron_variant	Intron 2 of 11		XP_047282891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS1	ENST00000350997.12	c.486+80G>A		intron_variant	Intron 2 of 11	1	NM_013402.7	ENSP00000322229.9

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

African (AFR) AF: 0.0678 AC: 1198 AN: 17658

American (AMR) AF: 0.627 AC: 23435 AN: 37348

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 4587 AN: 20928

East Asian (EAS) AF: 0.441 AC: 15984 AN: 36250

South Asian (SAS) AF: 0.154 AC: 10756 AN: 70034

European-Finnish (FIN) AF: 0.395 AC: 19950 AN: 50452

Middle Eastern (MID) AF: 0.238 AC: 1010 AN: 4246

European-Non Finnish (NFE) AF: 0.298 AC: 126604 AN: 424296

Other (OTH) AF: 0.318 AC: 11117 AN: 34994

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

African (AFR) AF: 0.0709 AC: 2941 AN: 41460

American (AMR) AF: 0.461 AC: 7029 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3468

East Asian (EAS) AF: 0.542 AC: 2798 AN: 5160

South Asian (SAS) AF: 0.163 AC: 786 AN: 4814

European-Finnish (FIN) AF: 0.395 AC: 4155 AN: 10524

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20150 AN: 67912

Other (OTH) AF: 0.304 AC: 643 AN: 2112

Alfa AF: 0.279 Hom.: 12805

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
PhyloP100		0.052
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs174556; hg19: chr11-61580635; COSMIC: COSV57246628; COSMIC: COSV57246628;