chr11-61803876-C-G

Variant names:

• chr11-61803876-C-G
• rs174548
• NM_013402.7:c.1054-109G>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.1054-109G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 807,702 control chromosomes in the GnomAD database, including 45,473 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 0.31 (8103 hom., cov: 32)
  • Exomes 𝑓: 0.32 (37370 hom.)
• Consequence: FADS1 NM_013402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 192 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FADS1	NM_013402.7	c.1054-109G>C		intron_variant	Intron 7 of 11	ENST00000350997.12	NP_037534.5
FADS1	XM_011545022.3	c.841-109G>C		intron_variant	Intron 7 of 11		XP_011543324.1
FADS1	XM_047426935.1	c.631-109G>C		intron_variant	Intron 7 of 11		XP_047282891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS1	ENST00000350997.12	c.1054-109G>C		intron_variant	Intron 7 of 11	1	NM_013402.7	ENSP00000322229.9

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46538 AN: 151900 Hom.: 8084 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.338

GnomAD4 exome AF: 0.318 AC: 208408 AN: 655684 Hom.: 37370 Cov.: 8 AF XY: 0.307 AC XY: 106334 AN XY: 346298

African (AFR) AF: 0.210 AC: 3679 AN: 17510

American (AMR) AF: 0.633 AC: 20742 AN: 32782

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 4333 AN: 18368

East Asian (EAS) AF: 0.441 AC: 14646 AN: 33246

South Asian (SAS) AF: 0.157 AC: 9423 AN: 60204

European-Finnish (FIN) AF: 0.401 AC: 17335 AN: 43242

Middle Eastern (MID) AF: 0.260 AC: 1053 AN: 4048

European-Non Finnish (NFE) AF: 0.305 AC: 125823 AN: 412670

Other (OTH) AF: 0.338 AC: 11374 AN: 33614

GnomAD4 genome AF: 0.306 AC: 46578 AN: 152018 Hom.: 8103 Cov.: 32 AF XY: 0.312 AC XY: 23181 AN XY: 74302

African (AFR) AF: 0.210 AC: 8699 AN: 41466

American (AMR) AF: 0.491 AC: 7502 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3470

East Asian (EAS) AF: 0.543 AC: 2810 AN: 5172

South Asian (SAS) AF: 0.165 AC: 794 AN: 4800

European-Finnish (FIN) AF: 0.398 AC: 4210 AN: 10566

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20686 AN: 67948

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

Alfa AF: 0.302 Hom.: 4203

Bravo AF: 0.315

Asia WGS AF: 0.369 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.35
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs174548; hg19: chr11-61571348; COSMIC: COSV107410222;