rs3834458

Variant names:

• chr11-61827448-CT-C
• rs3834458
• ENST00000257261.10:c.142-10329delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001281501.1(FADS2):​c.142-10329delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,130 control chromosomes in the GnomAD database, including 8,063 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (8053 hom., cov: 22)
  • Exomes 𝑓: 0.37 (10 hom.)
• Consequence: FADS2 NM_001281501.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 82 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]

FADS1 (HGNC:3574): (fatty acid desaturase 1) 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 FADS1 and FADS2 at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281501.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS2	NM_001281501.1		c.142-10329delT		intron	N/A	NP_001268430.1	O95864-2
	FADS2	NM_001281502.1		c.115-10329delT		intron	N/A	NP_001268431.1	O95864-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS2	ENST00000257261.10	TSL:1	c.142-10329delT		intron	N/A	ENSP00000257261.6	O95864-2
	FADS2	ENST00000522056.5	TSL:2	c.115-10329delT		intron	N/A	ENSP00000429500.1	O95864-4
	FADS1	ENST00000421879.5	TSL:3	c.-49+1752delA		intron	N/A	ENSP00000416043.1	C9JJB3

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43439 AN: 151888 Hom.: 8031 Cov.: 22

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.371 AC: 46 AN: 124 Hom.: 10 Cov.: 0 AF XY: 0.385 AC XY: 20 AN XY: 52

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 2 AN: 4

East Asian (EAS) AF: 0.400 AC: 4 AN: 10

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 15 AN: 30

Middle Eastern (MID) AF: 0.333 AC: 4 AN: 12

European-Non Finnish (NFE) AF: 0.269 AC: 14 AN: 52

Other (OTH) AF: 0.500 AC: 7 AN: 14

GnomAD4 genome AF: 0.286 AC: 43473 AN: 152006 Hom.: 8053 Cov.: 22 AF XY: 0.292 AC XY: 21676 AN XY: 74302

African (AFR) AF: 0.0781 AC: 3244 AN: 41520

American (AMR) AF: 0.486 AC: 7424 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 986 AN: 3470

East Asian (EAS) AF: 0.553 AC: 2841 AN: 5134

South Asian (SAS) AF: 0.179 AC: 863 AN: 4824

European-Finnish (FIN) AF: 0.418 AC: 4412 AN: 10554

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22675 AN: 67914

Other (OTH) AF: 0.338 AC: 715 AN: 2114

Alfa AF: 0.180 Hom.: 411

Bravo AF: 0.288

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.20
Mutation Taster		=97/3	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3834458; hg19: chr11-61594920;