rs174553

Positions:

• chr11-61807686-A-G
• chr11-61807686-A-T

Variant summary

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

The ENST00000350997.12(FADS1):​c.916-962T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,088 control chromosomes in the GnomAD database, including 8,132 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 0.29 (8132 hom., cov: 32)
• Consequence: FADS1 ENST00000350997.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299

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 = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FADS1	NM_013402.7	c.916-962T>C		intron_variant		ENST00000350997.12	NP_037534.5
FADS1	XM_011545022.3	c.703-962T>C		intron_variant			XP_011543324.1
FADS1	XM_047426935.1	c.493-962T>C		intron_variant			XP_047282891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS1	ENST00000350997.12	c.916-962T>C		intron_variant		1	NM_013402.7	ENSP00000322229	P1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43662 AN: 151970 Hom.: 8110 Cov.: 32

Gnomad AFR AF: 0.0782

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.287 AC: 43696 AN: 152088 Hom.: 8132 Cov.: 32 AF XY: 0.293 AC XY: 21795 AN XY: 74338

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.340

Alfa AF: 0.311 Hom.: 1042

Bravo AF: 0.288

Asia WGS AF: 0.375 AC: 1303 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	1.6
DANN	Benign	0.65

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: rs174553; hg19: chr11-61575158;