11-61812288-T-C

Position:

• chr11-61812288-T-C

Variant summary

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

The NM_013402.7(FADS1):​c.684+183A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,008 control chromosomes in the GnomAD database, including 6,886 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 0.26 (6886 hom., cov: 32)
• Consequence: FADS1 NM_013402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736

Genes affected

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]

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FADS1	NM_013402.7	c.684+183A>G		intron_variant		ENST00000350997.12
FADS1	XM_011545022.3	c.471+183A>G		intron_variant
FADS1	XM_047426935.1	c.261+183A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FADS1	ENST00000350997.12	c.684+183A>G		intron_variant		1	NM_013402.7	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39672 AN: 151890 Hom.: 6866 Cov.: 32

Gnomad AFR AF: 0.0712

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.261 AC: 39706 AN: 152008 Hom.: 6886 Cov.: 32 AF XY: 0.268 AC XY: 19906 AN XY: 74274

Gnomad4 AFR AF: 0.0710

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.304

Alfa AF: 0.133 Hom.: 333

Bravo AF: 0.263

Asia WGS AF: 0.359 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.048
DANN	Benign	0.36

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: rs174555; hg19: chr11-61579760;