rs2072113

Positions:

• chr11-61837495-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.208-283C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,168 control chromosomes in the GnomAD database, including 2,304 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 0.15 (2304 hom., cov: 32)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FADS2	NM_004265.4	c.208-283C>T		intron_variant		ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.142-283C>T		intron_variant			NP_001268430.1
FADS2	NM_001281502.1	c.115-283C>T		intron_variant			NP_001268431.1
FADS2	XM_047427889.1	c.208-283C>T		intron_variant			XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.208-283C>T		intron_variant		1	NM_004265.4	ENSP00000278840	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23508 AN: 152050 Hom.: 2293 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.155 AC: 23561 AN: 152168 Hom.: 2304 Cov.: 32 AF XY: 0.163 AC XY: 12128 AN XY: 74384

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.0747

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.160

Alfa AF: 0.152 Hom.: 271

Bravo AF: 0.154

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.043
DANN	Benign	0.63

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: rs2072113; hg19: chr11-61604967;