11-61857413-G-C

Variant names:

• chr11-61857413-G-C
• rs526126
• NM_004265.4:c.806-41G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004265.4(FADS2):​c.806-41G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 1,576,556 control chromosomes in the GnomAD database, including 515,138 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 0.69 (40007 hom., cov: 32)
  • Exomes 𝑓: 0.81 (475131 hom.)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361
• Publications: 35 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FADS2	NM_004265.4	c.806-41G>C		intron_variant	Intron 6 of 11	ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.740-41G>C		intron_variant	Intron 6 of 11		NP_001268430.1
FADS2	NM_001281502.1	c.713-41G>C		intron_variant	Intron 6 of 11		NP_001268431.1
FADS2	XM_047427889.1	c.806-41G>C		intron_variant	Intron 7 of 12		XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.806-41G>C		intron_variant	Intron 6 of 11	1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104794 AN: 151998 Hom.: 39987 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.712

GnomAD2 exomes AF: 0.810 AC: 202408 AN: 250024 AF XY: 0.820

Gnomad AFR exome AF: 0.319

Gnomad AMR exome AF: 0.879

Gnomad ASJ exome AF: 0.798

Gnomad EAS exome AF: 0.825

Gnomad FIN exome AF: 0.888

Gnomad NFE exome AF: 0.822

Gnomad OTH exome AF: 0.820

GnomAD4 exome AF: 0.812 AC: 1156607 AN: 1424440 Hom.: 475131 Cov.: 25 AF XY: 0.816 AC XY: 580201 AN XY: 711184

African (AFR) AF: 0.309 AC: 10088 AN: 32696

American (AMR) AF: 0.872 AC: 38940 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 20629 AN: 25926

East Asian (EAS) AF: 0.875 AC: 34583 AN: 39506

South Asian (SAS) AF: 0.888 AC: 75992 AN: 85530

European-Finnish (FIN) AF: 0.889 AC: 46048 AN: 51822

Middle Eastern (MID) AF: 0.795 AC: 4545 AN: 5714

European-Non Finnish (NFE) AF: 0.815 AC: 879562 AN: 1079384

Other (OTH) AF: 0.781 AC: 46220 AN: 59186

GnomAD4 genome AF: 0.689 AC: 104849 AN: 152116 Hom.: 40007 Cov.: 32 AF XY: 0.701 AC XY: 52113 AN XY: 74378

African (AFR) AF: 0.330 AC: 13705 AN: 41498

American (AMR) AF: 0.815 AC: 12465 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2716 AN: 3470

East Asian (EAS) AF: 0.839 AC: 4307 AN: 5134

South Asian (SAS) AF: 0.884 AC: 4266 AN: 4824

European-Finnish (FIN) AF: 0.891 AC: 9454 AN: 10612

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55531 AN: 67966

Other (OTH) AF: 0.714 AC: 1509 AN: 2112

Alfa AF: 0.734 Hom.: 5324

Bravo AF: 0.669

Asia WGS AF: 0.823 AC: 2862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.51
PhyloP100		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs526126; hg19: chr11-61624885; COSMIC: COSV53897648; COSMIC: COSV53897648;