11-61837310-A-T

Variant names:

• chr11-61837310-A-T
• rs2524299
• NM_004265.4:c.208-468A>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.208-468A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,084 control chromosomes in the GnomAD database, including 2,642 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 0.17 (2642 hom., cov: 33)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917
• Publications: 36 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004265.4. 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_004265.4	MANE Select	c.208-468A>T		intron	N/A	NP_004256.1	O95864-1
	FADS2	NM_001281501.1		c.142-468A>T		intron	N/A	NP_001268430.1	O95864-2
	FADS2	NM_001281502.1		c.115-468A>T		intron	N/A	NP_001268431.1	O95864-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS2	ENST00000278840.9	TSL:1 MANE Select	c.208-468A>T		intron	N/A	ENSP00000278840.4	O95864-1
	FADS2	ENST00000257261.10	TSL:1	c.142-468A>T		intron	N/A	ENSP00000257261.6	O95864-2
	FADS2	ENST00000521849.5	TSL:1	c.208-468A>T		intron	N/A	ENSP00000431091.1	O95864-3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25643 AN: 151966 Hom.: 2629 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.169 AC: 25703 AN: 152084 Hom.: 2642 Cov.: 33 AF XY: 0.177 AC XY: 13161 AN XY: 74330

African (AFR) AF: 0.166 AC: 6877 AN: 41494

American (AMR) AF: 0.248 AC: 3785 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2127 AN: 5172

South Asian (SAS) AF: 0.0748 AC: 360 AN: 4812

European-Finnish (FIN) AF: 0.284 AC: 3006 AN: 10566

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.127 AC: 8662 AN: 67978

Other (OTH) AF: 0.173 AC: 365 AN: 2110

Alfa AF: 0.163 Hom.: 290

Bravo AF: 0.170

Asia WGS AF: 0.239 AC: 830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.37
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2524299; hg19: chr11-61604782;