rs75810419

chr11-61815055-C-Achr11-61815055-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_013402.7(FADS1):c.375+1500G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 155,746 control chromosomes in the GnomAD database, including 102 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 0.025 (95 hom., cov: 32)
  • Exomes 𝑓: 0.043 (7 hom.)
• Consequence: FADS1 NM_013402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309

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=-0.73).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0249 (3788/152342) while in subpopulation NFE AF= 0.0297 (2021/68022). AF 95% confidence interval is 0.0286. There are 95 homozygotes in gnomad4. There are 2027 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 95 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FADS1	NM_013402.7	c.375+1500G>T		intron_variant		ENST00000350997.12
FADS1	XM_047426935.1	c.-462G>T		5_prime_UTR_variant	1/12
FADS1	XM_011545022.3	c.162+19G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FADS1	ENST00000350997.12	c.375+1500G>T		intron_variant		1	NM_013402.7	P1

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3788 AN: 152224 Hom.: 95 Cov.: 32

Gnomad AFR AF: 0.00760

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.00539

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0210

GnomAD4 exome AF: 0.0435 AC: 148 AN: 3404 Hom.: 7 Cov.: 0 AF XY: 0.0438 AC XY: 81 AN XY: 1848

Gnomad4 AFR exome AF: 0.0132

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0273

Gnomad4 SAS exome AF: 0.0111

Gnomad4 FIN exome AF: 0.0620

Gnomad4 NFE exome AF: 0.0180

Gnomad4 OTH exome AF: 0.0240

GnomAD4 genome AF: 0.0249 AC: 3788 AN: 152342 Hom.: 95 Cov.: 32 AF XY: 0.0272 AC XY: 2027 AN XY: 74494

Gnomad4 AFR AF: 0.00757

Gnomad4 AMR AF: 0.0189

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.00541

Gnomad4 SAS AF: 0.0159

Gnomad4 FIN AF: 0.0807

Gnomad4 NFE AF: 0.0297

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0145 Hom.: 7

Bravo AF: 0.0188

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	7.8
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs75810419; hg19: chr11-61582527;