11-61801834-C-G

Variant names:

• chr11-61801834-C-G
• rs174545
• NM_013402.7:c.*577G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 118 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013402.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS1	NM_013402.7	MANE Select	c.*577G>C		3_prime_UTR	Exon 12 of 12	NP_037534.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS1	ENST00000350997.12	TSL:1 MANE Select	c.*577G>C		3_prime_UTR	Exon 12 of 12	ENSP00000322229.9	A0A0A0MR51
	FADS1	ENST00000935427.1		c.*577G>C		3_prime_UTR	Exon 12 of 12	ENSP00000605486.1
	FADS1	ENST00000935426.1		c.*577G>C		3_prime_UTR	Exon 11 of 11	ENSP00000605485.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.526 AC: 61 AN: 116

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.290 AC: 40 AN: 138

South Asian (SAS) AF: 0.0556 AC: 1 AN: 18

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.259 AC: 137 AN: 528

Other (OTH) AF: 0.111 AC: 2 AN: 18

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

African (AFR) AF: 0.0780 AC: 3234 AN: 41484

American (AMR) AF: 0.488 AC: 7449 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 994 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2861 AN: 5150

South Asian (SAS) AF: 0.179 AC: 863 AN: 4812

European-Finnish (FIN) AF: 0.419 AC: 4403 AN: 10500

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22831 AN: 67960

Other (OTH) AF: 0.341 AC: 720 AN: 2110

Alfa AF: 0.312 Hom.: 1105

Bravo AF: 0.288

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Benign	0.82
PhyloP100		0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs174545; hg19: chr11-61569306;