rs174550

Variant names:

• chr11-61804006-T-C
• rs174550
• NM_013402.7:c.1054-239A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013402.7(FADS1):​c.1054-239A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 559,836 control chromosomes in the GnomAD database, including 33,387 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 (8139 hom., cov: 32)
  • Exomes 𝑓: 0.33 (25248 hom.)
• Consequence: FADS1 NM_013402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591
• Publications: 277 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 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.1054-239A>G		intron	N/A	NP_037534.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS1	ENST00000350997.12	TSL:1 MANE Select	c.1054-239A>G		intron	N/A	ENSP00000322229.9	A0A0A0MR51
	FADS1	ENST00000460649.5	TSL:2	c.-251A>G		5_prime_UTR	Exon 1 of 5	ENSP00000445253.1	F5H3P6
	FADS1	ENST00000935427.1		c.1054-239A>G		intron	N/A	ENSP00000605486.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43663 AN: 151954 Hom.: 8117 Cov.: 32

Gnomad AFR AF: 0.0782

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.334 AC: 136336 AN: 407764 Hom.: 25248 Cov.: 0 AF XY: 0.324 AC XY: 69897 AN XY: 215458

African (AFR) AF: 0.0767 AC: 887 AN: 11560

American (AMR) AF: 0.588 AC: 9456 AN: 16076

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 3532 AN: 12524

East Asian (EAS) AF: 0.446 AC: 12604 AN: 28236

South Asian (SAS) AF: 0.174 AC: 7429 AN: 42584

European-Finnish (FIN) AF: 0.423 AC: 11000 AN: 26024

Middle Eastern (MID) AF: 0.248 AC: 442 AN: 1782

European-Non Finnish (NFE) AF: 0.337 AC: 82639 AN: 245486

Other (OTH) AF: 0.355 AC: 8347 AN: 23492

GnomAD4 genome AF: 0.287 AC: 43697 AN: 152072 Hom.: 8139 Cov.: 32 AF XY: 0.293 AC XY: 21792 AN XY: 74322

African (AFR) AF: 0.0780 AC: 3240 AN: 41542

American (AMR) AF: 0.487 AC: 7440 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 994 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2861 AN: 5166

South Asian (SAS) AF: 0.180 AC: 865 AN: 4818

European-Finnish (FIN) AF: 0.421 AC: 4439 AN: 10550

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

European-Non Finnish (NFE) AF: 0.336 AC: 22824 AN: 67944

Other (OTH) AF: 0.340 AC: 719 AN: 2112

Alfa AF: 0.324 Hom.: 35796

Bravo AF: 0.288

Asia WGS AF: 0.375 AC: 1303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.85
PhyloP100		-0.59
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs174550;

hg19: chr11-61571478;