rs174583

chr11-61842278-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.618+1553C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,194 control chromosomes in the GnomAD database, including 10,272 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 (10272 hom., cov: 33)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34

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=-0.48).
• 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/exons	MANE	UniProt
FADS2	NM_004265.4	c.618+1553C>T		intron_variant		ENST00000278840.9
FADS2	NM_001281501.1	c.552+1553C>T		intron_variant
FADS2	NM_001281502.1	c.525+1553C>T		intron_variant
FADS2	XM_047427889.1	c.618+1553C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FADS2	ENST00000278840.9	c.618+1553C>T		intron_variant		1	NM_004265.4	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53601 AN: 152076 Hom.: 10239 Cov.: 33

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.353 AC: 53677 AN: 152194 Hom.: 10272 Cov.: 33 AF XY: 0.357 AC XY: 26558 AN XY: 74408

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.390

Alfa AF: 0.349 Hom.: 17495

Bravo AF: 0.361

Asia WGS AF: 0.403 AC: 1399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	0.29
Dann	Benign	0.90

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: rs174583; hg19: chr11-61609750;