rs174561

Variant names:

• chr11-61815236-T-C
• rs174561
• NM_013402.7:c.375+1319A>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.375+1319A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 166,768 control chromosomes in the GnomAD database, including 7,934 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 (6894 hom., cov: 33)
  • Exomes 𝑓: 0.36 (1040 hom.)
• Consequence: FADS1 NM_013402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 137 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]

MIR1908 (HGNC:35392): (microRNA 1908) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 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.375+1319A>G		intron	N/A	NP_037534.5
	MIR1908	NR_031729.1		n.5A>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS1	ENST00000350997.12	TSL:1 MANE Select	c.375+1319A>G		intron	N/A	ENSP00000322229.9	A0A0A0MR51
	FADS1	ENST00000542506.5	TSL:2	c.-489A>G		5_prime_UTR	Exon 1 of 12	ENSP00000441403.1	O60427-2
	FADS1	ENST00000935427.1		c.375+1319A>G		intron	N/A	ENSP00000605486.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39712 AN: 151984 Hom.: 6875 Cov.: 33

Gnomad AFR AF: 0.0714

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.301

GnomAD2 exomes AF: 0.309 AC: 5996 AN: 19432 AF XY: 0.320

Gnomad AFR exome AF: 0.0682

Gnomad AMR exome AF: 0.514

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.615

Gnomad FIN exome AF: 0.374

Gnomad NFE exome AF: 0.282

Gnomad OTH exome AF: 0.308

GnomAD4 exome AF: 0.363 AC: 5324 AN: 14666 Hom.: 1040 Cov.: 0 AF XY: 0.369 AC XY: 2641 AN XY: 7154

African (AFR) AF: 0.0972 AC: 7 AN: 72

American (AMR) AF: 0.500 AC: 5 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.237 AC: 9 AN: 38

South Asian (SAS) AF: 0.103 AC: 8 AN: 78

European-Finnish (FIN) AF: 0.383 AC: 4784 AN: 12494

Middle Eastern (MID) AF: 0.251 AC: 359 AN: 1432

European-Non Finnish (NFE) AF: 0.325 AC: 95 AN: 292

Other (OTH) AF: 0.232 AC: 57 AN: 246

GnomAD4 genome AF: 0.261 AC: 39745 AN: 152102 Hom.: 6894 Cov.: 33 AF XY: 0.268 AC XY: 19940 AN XY: 74358

African (AFR) AF: 0.0713 AC: 2959 AN: 41528

American (AMR) AF: 0.461 AC: 7056 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 764 AN: 3468

East Asian (EAS) AF: 0.542 AC: 2783 AN: 5138

South Asian (SAS) AF: 0.163 AC: 787 AN: 4824

European-Finnish (FIN) AF: 0.395 AC: 4187 AN: 10590

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

European-Non Finnish (NFE) AF: 0.299 AC: 20284 AN: 67942

Other (OTH) AF: 0.303 AC: 640 AN: 2110

Alfa AF: 0.278 Hom.: 862

Bravo AF: 0.263

Asia WGS AF: 0.358 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		0.094
PromoterAI		-0.11	Neutral
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: rs174561; hg19: chr11-61582708; COSMIC: COSV57246036; COSMIC: COSV57246036;