rs174547

Positions:

• chr11-61803311-T-C

Variant summary

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

The NM_013402.7(FADS1):​c.1248+52A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,472,252 control chromosomes in the GnomAD database, including 90,604 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 0.29 (8147 hom., cov: 32)
  • Exomes 𝑓: 0.34 (82457 hom.)
• Consequence: FADS1 NM_013402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366

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=-0.88).
• 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
FADS1	NM_013402.7	c.1248+52A>G		intron_variant		ENST00000350997.12	NP_037534.5
FADS1	XM_011545022.3	c.1035+52A>G		intron_variant			XP_011543324.1
FADS1	XM_047426935.1	c.825+52A>G		intron_variant			XP_047282891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS1	ENST00000350997.12	c.1248+52A>G		intron_variant		1	NM_013402.7	ENSP00000322229	P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43701 AN: 151986 Hom.: 8125 Cov.: 32

Gnomad AFR AF: 0.0782

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.338 AC: 446677 AN: 1320148 Hom.: 82457 Cov.: 20 AF XY: 0.332 AC XY: 220249 AN XY: 664042

Gnomad4 AFR exome AF: 0.0617

Gnomad4 AMR exome AF: 0.650

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.339

Gnomad4 OTH exome AF: 0.345

GnomAD4 genome AF: 0.288 AC: 43735 AN: 152104 Hom.: 8147 Cov.: 32 AF XY: 0.293 AC XY: 21819 AN XY: 74354

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.339

Alfa AF: 0.327 Hom.: 16839

Bravo AF: 0.288

Asia WGS AF: 0.375 AC: 1302 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	7.1
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs174547; hg19: chr11-61570783; COSMIC: COSV63520556; COSMIC: COSV63520556;