rs174546

Variant names:

• chr11-61802358-C-T
• rs174546
• NM_013402.7:c.*53G>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.*53G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,490,570 control chromosomes in the GnomAD database, including 90,175 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 (8149 hom., cov: 32)
  • Exomes 𝑓: 0.34 (82026 hom.)
• Consequence: FADS1 NM_013402.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419
• Publications: 374 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=-0.55).
• 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 rank	MANE	Protein	UniProt
FADS1	NM_013402.7	c.*53G>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000350997.12	NP_037534.5
FADS1	XM_011545022.3	c.*53G>A		3_prime_UTR_variant	Exon 12 of 12		XP_011543324.1
FADS1	XM_047426935.1	c.*53G>A		3_prime_UTR_variant	Exon 12 of 12		XP_047282891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS1	ENST00000350997.12	c.*53G>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_013402.7	ENSP00000322229.9

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43680 AN: 152002 Hom.: 8127 Cov.: 32

Gnomad AFR AF: 0.0780

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: 452022 AN: 1338450 Hom.: 82026 Cov.: 21 AF XY: 0.332 AC XY: 220719 AN XY: 664056

African (AFR) AF: 0.0603 AC: 1841 AN: 30528

American (AMR) AF: 0.633 AC: 22707 AN: 35900

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 6915 AN: 24782

East Asian (EAS) AF: 0.456 AC: 16348 AN: 35878

South Asian (SAS) AF: 0.171 AC: 13356 AN: 78002

European-Finnish (FIN) AF: 0.424 AC: 20856 AN: 49190

Middle Eastern (MID) AF: 0.256 AC: 1425 AN: 5570

European-Non Finnish (NFE) AF: 0.341 AC: 349122 AN: 1022540

Other (OTH) AF: 0.347 AC: 19452 AN: 56060

GnomAD4 genome AF: 0.287 AC: 43714 AN: 152120 Hom.: 8149 Cov.: 32 AF XY: 0.293 AC XY: 21808 AN XY: 74340

African (AFR) AF: 0.0778 AC: 3230 AN: 41532

American (AMR) AF: 0.488 AC: 7454 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 994 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2856 AN: 5156

South Asian (SAS) AF: 0.179 AC: 864 AN: 4824

European-Finnish (FIN) AF: 0.421 AC: 4445 AN: 10564

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22840 AN: 67972

Other (OTH) AF: 0.340 AC: 717 AN: 2110

Alfa AF: 0.322 Hom.: 38223

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	-0.55
CADD	Benign	7.3
DANN	Benign	0.78
PhyloP100		0.42
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: rs174546; hg19: chr11-61569830; COSMIC: COSV63520553; COSMIC: COSV63520553;