rs174589

chr11-61848331-C-Gchr11-61848331-C-T

Variant summary

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

The NM_004265.4(FADS2):c.744+47C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,609,918 control chromosomes in the GnomAD database, including 33,454 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 0.15 (2329 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31125 hom.)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

Genes affected

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]

LOC124902679 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FADS2	NM_004265.4	c.744+47C>G		intron_variant		ENST00000278840.9
LOC124902679	XR_007062695.1	n.41C>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FADS2	ENST00000278840.9	c.744+47C>G		intron_variant		1	NM_004265.4	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23398 AN: 152000 Hom.: 2332 Cov.: 32

Gnomad AFR AF: 0.0458

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.182

GnomAD3 exomes AF: 0.188 AC: 47248 AN: 250656 Hom.: 5456 AF XY: 0.183 AC XY: 24833 AN XY: 135412

Gnomad AFR exome AF: 0.0432

Gnomad AMR exome AF: 0.354

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.139

Gnomad SAS exome AF: 0.117

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.199 AC: 290152 AN: 1457800 Hom.: 31125 Cov.: 31 AF XY: 0.197 AC XY: 142469 AN XY: 724974

Gnomad4 AFR exome AF: 0.0366

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.154 AC: 23392 AN: 152118 Hom.: 2329 Cov.: 32 AF XY: 0.151 AC XY: 11225 AN XY: 74356

Gnomad4 AFR AF: 0.0457

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.182

Alfa AF: 0.115 Hom.: 250

Bravo AF: 0.159

Asia WGS AF: 0.150 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.12
Dann	Benign	0.54

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: rs174589; hg19: chr11-61615803; COSMIC: COSV53898801; COSMIC: COSV53898801;