rs174561

Positions:

• chr11-61815236-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.375+1319A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 166,768 control chromosomes in the GnomAD database, including 7,934 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 (6894 hom., cov: 33)
  • Exomes 𝑓: 0.36 (1040 hom.)
• Consequence: FADS1 NM_013402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

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]

MIR1908 (HGNC:35392): (microRNA 1908) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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=-0.77).
• 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/exons	MANE	Protein	UniProt
FADS1	NM_013402.7	c.375+1319A>G		intron_variant		ENST00000350997.12	NP_037534.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS1	ENST00000350997.12	c.375+1319A>G		intron_variant		1	NM_013402.7	ENSP00000322229.9

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39712 AN: 151984 Hom.: 6875 Cov.: 33

Gnomad AFR AF: 0.0714

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.301

GnomAD3 exomes AF: 0.309 AC: 5996 AN: 19432 Hom.: 1039 AF XY: 0.320 AC XY: 2934 AN XY: 9166

Gnomad AFR exome AF: 0.0682

Gnomad AMR exome AF: 0.514

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.615

Gnomad SAS exome AF: 0.107

Gnomad FIN exome AF: 0.374

Gnomad NFE exome AF: 0.282

Gnomad OTH exome AF: 0.308

GnomAD4 exome AF: 0.363 AC: 5324 AN: 14666 Hom.: 1040 Cov.: 0 AF XY: 0.369 AC XY: 2641 AN XY: 7154

Gnomad4 AFR exome AF: 0.0972

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.383

Gnomad4 NFE exome AF: 0.325

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.261 AC: 39745 AN: 152102 Hom.: 6894 Cov.: 33 AF XY: 0.268 AC XY: 19940 AN XY: 74358

Gnomad4 AFR AF: 0.0713

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.303

Alfa AF: 0.278 Hom.: 862

Bravo AF: 0.263

Asia WGS AF: 0.358 AC: 1243 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	11
DANN	Benign	0.69

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: rs174561; hg19: chr11-61582708; COSMIC: COSV57246036; COSMIC: COSV57246036;