rs174544

Positions:

• chr11-61800281-C-A
• chr11-61800281-C-G

Variant summary

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

The NM_013402.7(FADS1):​c.*2130G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,650 control chromosomes in the GnomAD database, including 6,802 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 (6795 hom., cov: 31)
  • Exomes 𝑓: 0.28 (7 hom.)
• Consequence: FADS1 NM_013402.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FADS1	NM_013402.7	c.*2130G>T		3_prime_UTR_variant	12/12	ENST00000350997.12	NP_037534.5
FADS1	XM_011545022.3	c.*2130G>T		3_prime_UTR_variant	12/12		XP_011543324.1
FADS1	XM_047426935.1	c.*2130G>T		3_prime_UTR_variant	12/12		XP_047282891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS1	ENST00000350997.12	c.*2130G>T		3_prime_UTR_variant	12/12	1	NM_013402.7	ENSP00000322229.9
FADS2	ENST00000574708.5	n.49+7253C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39360 AN: 151352 Hom.: 6775 Cov.: 31

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.278 AC: 50 AN: 180 Hom.: 7 Cov.: 0 AF XY: 0.313 AC XY: 35 AN XY: 112

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.261

Gnomad4 NFE exome AF: 0.353

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.260 AC: 39394 AN: 151470 Hom.: 6795 Cov.: 31 AF XY: 0.267 AC XY: 19747 AN XY: 73990

Gnomad4 AFR AF: 0.0710

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.304

Alfa AF: 0.274 Hom.: 822

Bravo AF: 0.263

Asia WGS AF: 0.356 AC: 1235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.0
DANN	Benign	0.86

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: rs174544; hg19: chr11-61567753;