NM_004265.4:c.208-1740C>A

Variant names:

• chr11-61836038-C-A
• rs174576
• NM_004265.4:c.208-1740C>A

Variant summary

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

The NM_004265.4(FADS2):​c.208-1740C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,086 control chromosomes in the GnomAD database, including 10,070 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 0.35 (10070 hom., cov: 33)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 133 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FADS2	NM_004265.4	c.208-1740C>A		intron_variant	Intron 1 of 11	ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.142-1740C>A		intron_variant	Intron 1 of 11		NP_001268430.1
FADS2	NM_001281502.1	c.115-1740C>A		intron_variant	Intron 1 of 11		NP_001268431.1
FADS2	XM_047427889.1	c.208-1740C>A		intron_variant	Intron 2 of 12		XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.208-1740C>A		intron_variant	Intron 1 of 11	1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53059 AN: 151968 Hom.: 10038 Cov.: 33

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.384

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.349 AC: 53127 AN: 152086 Hom.: 10070 Cov.: 33 AF XY: 0.353 AC XY: 26241 AN XY: 74328

African (AFR) AF: 0.276 AC: 11459 AN: 41500

American (AMR) AF: 0.518 AC: 7920 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3470

East Asian (EAS) AF: 0.555 AC: 2869 AN: 5170

South Asian (SAS) AF: 0.184 AC: 887 AN: 4826

European-Finnish (FIN) AF: 0.422 AC: 4447 AN: 10550

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23333 AN: 67970

Other (OTH) AF: 0.387 AC: 816 AN: 2110

Alfa AF: 0.347 Hom.: 29153

Bravo AF: 0.358

Asia WGS AF: 0.391 AC: 1359 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	0.24
DANN	Benign	0.45
PhyloP100		-1.5
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: rs174576; hg19: chr11-61603510;