11-61837310-A-T

Position:

• chr11-61837310-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004265.4(FADS2):​c.208-468A>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

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=-0.91).
• 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/exons	MANE	Protein	UniProt
FADS2	NM_004265.4	c.208-468A>T		intron_variant		ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.142-468A>T		intron_variant			NP_001268430.1
FADS2	NM_001281502.1	c.115-468A>T		intron_variant			NP_001268431.1
FADS2	XM_047427889.1	c.208-468A>T		intron_variant			XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.208-468A>T		intron_variant		1	NM_004265.4	ENSP00000278840.4

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

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.0748

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.173

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs2524299; hg19: chr11-61604782;