rs174549

Positions:

• chr11-61803910-G-A
• chr11-61803910-G-C
• chr11-61803910-G-T

Variant summary

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

The NM_013402.7(FADS1):​c.1054-143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 659,588 control chromosomes in the GnomAD database, including 34,651 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 (6920 hom., cov: 32)
  • Exomes 𝑓: 0.31 (27731 hom.)
• Consequence: FADS1 NM_013402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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]

FADS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FADS1	NM_013402.7	c.1054-143C>T		intron_variant		ENST00000350997.12	NP_037534.5
FADS1	XM_011545022.3	c.841-143C>T		intron_variant			XP_011543324.1
FADS1	XM_047426935.1	c.631-143C>T		intron_variant			XP_047282891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS1	ENST00000350997.12	c.1054-143C>T		intron_variant		1	NM_013402.7	ENSP00000322229.9

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39795 AN: 151918 Hom.: 6900 Cov.: 32

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.309 AC: 156785 AN: 507552 Hom.: 27731 Cov.: 5 AF XY: 0.298 AC XY: 80546 AN XY: 269998

Gnomad4 AFR exome AF: 0.0702

Gnomad4 AMR exome AF: 0.603

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.439

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.321

GnomAD4 genome AF: 0.262 AC: 39829 AN: 152036 Hom.: 6920 Cov.: 32 AF XY: 0.269 AC XY: 19964 AN XY: 74288

Gnomad4 AFR AF: 0.0713

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.305

Alfa AF: 0.283 Hom.: 1456

Bravo AF: 0.264

Asia WGS AF: 0.359 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs174549; hg19: chr11-61571382;