11-61801834-C-G

Position:

• chr11-61801834-C-G

Variant summary

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

The NM_013402.7(FADS1):​c.*577G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,780 control chromosomes in the GnomAD database, including 8,191 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 (8140 hom., cov: 32)
  • Exomes 𝑓: 0.29 (51 hom.)
• Consequence: FADS1 NM_013402.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FADS1	NM_013402.7	c.*577G>C		3_prime_UTR_variant	12/12	ENST00000350997.12	NP_037534.5
FADS1	XM_011545022.3	c.*577G>C		3_prime_UTR_variant	12/12		XP_011543324.1
FADS1	XM_047426935.1	c.*577G>C		3_prime_UTR_variant	12/12		XP_047282891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS1	ENST00000350997.12	c.*577G>C		3_prime_UTR_variant	12/12	1	NM_013402.7	ENSP00000322229.9
FADS2	ENST00000574708.5	n.49+8806C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43635 AN: 151846 Hom.: 8118 Cov.: 32

Gnomad AFR AF: 0.0782

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.338

GnomAD4 exome AF: 0.295 AC: 241 AN: 818 Hom.: 51 Cov.: 0 AF XY: 0.303 AC XY: 126 AN XY: 416

Gnomad4 AMR exome AF: 0.526

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.0556

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.287 AC: 43669 AN: 151962 Hom.: 8140 Cov.: 32 AF XY: 0.293 AC XY: 21765 AN XY: 74238

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.341

Alfa AF: 0.312 Hom.: 1105

Bravo AF: 0.288

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs174545; hg19: chr11-61569306;