rs174589

Variant names:

• chr11-61848331-C-G
• rs174589
• NM_004265.4:c.744+47C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-61848331-C-G
• chr11-61848331-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FADS2	NM_004265.4	c.744+47C>G		intron_variant	Intron 5 of 11	ENST00000278840.9	NP_004256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.744+47C>G		intron_variant	Intron 5 of 11	1	NM_004265.4	ENSP00000278840.4

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

GnomAD2 exomes AF: 0.188 AC: 47248 AN: 250656 AF XY: 0.183

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 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

African (AFR) AF: 0.0366 AC: 1223 AN: 33416

American (AMR) AF: 0.346 AC: 15447 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 3623 AN: 26016

East Asian (EAS) AF: 0.115 AC: 4550 AN: 39590

South Asian (SAS) AF: 0.118 AC: 10143 AN: 86118

European-Finnish (FIN) AF: 0.132 AC: 7060 AN: 53314

Middle Eastern (MID) AF: 0.153 AC: 882 AN: 5748

European-Non Finnish (NFE) AF: 0.213 AC: 235985 AN: 1108742

Other (OTH) AF: 0.187 AC: 11239 AN: 60198

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

African (AFR) AF: 0.0457 AC: 1894 AN: 41488

American (AMR) AF: 0.259 AC: 3954 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3472

East Asian (EAS) AF: 0.143 AC: 738 AN: 5170

South Asian (SAS) AF: 0.116 AC: 557 AN: 4820

European-Finnish (FIN) AF: 0.129 AC: 1369 AN: 10586

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.203 AC: 13797 AN: 67982

Other (OTH) AF: 0.182 AC: 383 AN: 2110

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
PhyloP100		-0.17
Mutation Taster		=25/75	disease causing

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