chr11-61803910-G-A

Variant names:

• chr11-61803910-G-A
• rs174549
• NM_013402.7:c.1054-143C>T

Variant summary

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

The NM_013402.7(FADS1):​c.1054-143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 659,588 control chromosomes in the GnomAD database, including 34,651 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 0.26 (6920 hom., cov: 32)
  • Exomes 𝑓: 0.31 (27731 hom.)
• Consequence: FADS1 NM_013402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 142 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 = 0.526 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS1	NM_013402.7	MANE Select	c.1054-143C>T		intron	N/A	NP_037534.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS1	ENST00000350997.12	TSL:1 MANE Select	c.1054-143C>T		intron	N/A	ENSP00000322229.9
	FADS1	ENST00000460649.5	TSL:2	c.-155C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000445253.1
	FADS1	ENST00000460649.5	TSL:2	c.-155C>T		5_prime_UTR	Exon 1 of 5	ENSP00000445253.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39795 AN: 151918 Hom.: 6900 Cov.: 32

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.309 AC: 156785 AN: 507552 Hom.: 27731 Cov.: 5 AF XY: 0.298 AC XY: 80546 AN XY: 269998

African (AFR) AF: 0.0702 AC: 1000 AN: 14254

American (AMR) AF: 0.603 AC: 16388 AN: 27156

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 3441 AN: 15740

East Asian (EAS) AF: 0.439 AC: 13930 AN: 31702

South Asian (SAS) AF: 0.157 AC: 8068 AN: 51480

European-Finnish (FIN) AF: 0.400 AC: 14273 AN: 35654

Middle Eastern (MID) AF: 0.236 AC: 762 AN: 3234

European-Non Finnish (NFE) AF: 0.299 AC: 89808 AN: 299962

Other (OTH) AF: 0.321 AC: 9115 AN: 28370

GnomAD4 genome AF: 0.262 AC: 39829 AN: 152036 Hom.: 6920 Cov.: 32 AF XY: 0.269 AC XY: 19964 AN XY: 74288

African (AFR) AF: 0.0713 AC: 2960 AN: 41524

American (AMR) AF: 0.462 AC: 7053 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 773 AN: 3468

East Asian (EAS) AF: 0.542 AC: 2804 AN: 5170

South Asian (SAS) AF: 0.163 AC: 782 AN: 4812

European-Finnish (FIN) AF: 0.397 AC: 4185 AN: 10530

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20343 AN: 67946

Other (OTH) AF: 0.305 AC: 644 AN: 2110

Alfa AF: 0.285 Hom.: 10955

Bravo AF: 0.264

Asia WGS AF: 0.359 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.45
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=298/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs174549; hg19: chr11-61571382; COSMIC: COSV107410223;