NM_004265.4:c.208-2013C>T

Variant names:

• chr11-61835765-C-T
• rs2727270
• NM_004265.4:c.208-2013C>T

Variant summary

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

The NM_004265.4(FADS2):​c.208-2013C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,052 control chromosomes in the GnomAD database, including 1,945 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 0.13 (1945 hom., cov: 31)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.296
• Publications: 63 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FADS2	NM_004265.4	c.208-2013C>T		intron_variant	Intron 1 of 11	ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.142-2013C>T		intron_variant	Intron 1 of 11		NP_001268430.1
FADS2	NM_001281502.1	c.115-2013C>T		intron_variant	Intron 1 of 11		NP_001268431.1
FADS2	XM_047427889.1	c.208-2013C>T		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.208-2013C>T		intron_variant	Intron 1 of 11	1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19349 AN: 151934 Hom.: 1935 Cov.: 31

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.127 AC: 19383 AN: 152052 Hom.: 1945 Cov.: 31 AF XY: 0.137 AC XY: 10172 AN XY: 74312

African (AFR) AF: 0.0331 AC: 1372 AN: 41510

American (AMR) AF: 0.224 AC: 3424 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 366 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2122 AN: 5160

South Asian (SAS) AF: 0.0749 AC: 361 AN: 4818

European-Finnish (FIN) AF: 0.283 AC: 2981 AN: 10536

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8390 AN: 67970

Other (OTH) AF: 0.142 AC: 300 AN: 2110

Alfa AF: 0.124 Hom.: 5482

Bravo AF: 0.123

Asia WGS AF: 0.230 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.3
DANN	Benign	0.84
PhyloP100		0.30
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: rs2727270; hg19: chr11-61603237;