rs174578

Positions:

• chr11-61838027-T-A

Variant summary

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

The NM_004265.4(FADS2):​c.318+139T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 652,516 control chromosomes in the GnomAD database, including 46,733 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 0.38 (11535 hom., cov: 31)
  • Exomes 𝑓: 0.36 (35198 hom.)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FADS2	NM_004265.4	c.318+139T>A		intron_variant		ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.252+139T>A		intron_variant			NP_001268430.1
FADS2	NM_001281502.1	c.225+139T>A		intron_variant			NP_001268431.1
FADS2	XM_047427889.1	c.318+139T>A		intron_variant			XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.318+139T>A		intron_variant		1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57287 AN: 151678 Hom.: 11500 Cov.: 31

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.358 AC: 179043 AN: 500720 Hom.: 35198 AF XY: 0.345 AC XY: 91266 AN XY: 264700

Gnomad4 AFR exome AF: 0.374

Gnomad4 AMR exome AF: 0.663

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.446

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.427

Gnomad4 NFE exome AF: 0.344

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.378 AC: 57355 AN: 151796 Hom.: 11535 Cov.: 31 AF XY: 0.380 AC XY: 28206 AN XY: 74166

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.407

Alfa AF: 0.366 Hom.: 1325

Bravo AF: 0.392

Asia WGS AF: 0.395 AC: 1372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.55

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: rs174578; hg19: chr11-61605499;