rs75810419

Variant names:

• chr11-61815055-C-A
• rs75810419
• NM_013402.7:c.375+1500G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-61815055-C-A
• chr11-61815055-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_013402.7(FADS1):​c.375+1500G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 155,746 control chromosomes in the GnomAD database, including 102 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 0.025 (95 hom., cov: 32)
  • Exomes 𝑓: 0.043 (7 hom.)
• Consequence: FADS1 NM_013402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309
• Publications: 4 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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0249 (3788/152342) while in subpopulation NFE AF = 0.0297 (2021/68022). AF 95% confidence interval is 0.0286. There are 95 homozygotes in GnomAd4. There are 2027 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 95 AR gene

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.375+1500G>T		intron	N/A	NP_037534.5
	MIR1908	NR_031729.1		n.*106G>T		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS1	ENST00000350997.12	TSL:1 MANE Select	c.375+1500G>T		intron	N/A	ENSP00000322229.9
	FADS1	ENST00000541683.1	TSL:2	n.1128G>T		non_coding_transcript_exon	Exon 2 of 2
	FADS1	ENST00000542506.5	TSL:2	c.-308G>T		5_prime_UTR	Exon 1 of 12	ENSP00000441403.1

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3788 AN: 152224 Hom.: 95 Cov.: 32

Gnomad AFR AF: 0.00760

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.00539

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0210

GnomAD4 exome AF: 0.0435 AC: 148 AN: 3404 Hom.: 7 Cov.: 0 AF XY: 0.0438 AC XY: 81 AN XY: 1848

African (AFR) AF: 0.0132 AC: 1 AN: 76

American (AMR) AF: 0.00 AC: 0 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8

East Asian (EAS) AF: 0.0273 AC: 3 AN: 110

South Asian (SAS) AF: 0.0111 AC: 1 AN: 90

European-Finnish (FIN) AF: 0.0620 AC: 59 AN: 952

Middle Eastern (MID) AF: 0.0451 AC: 73 AN: 1618

European-Non Finnish (NFE) AF: 0.0180 AC: 6 AN: 334

Other (OTH) AF: 0.0240 AC: 5 AN: 208

GnomAD4 genome AF: 0.0249 AC: 3788 AN: 152342 Hom.: 95 Cov.: 32 AF XY: 0.0272 AC XY: 2027 AN XY: 74494

African (AFR) AF: 0.00757 AC: 315 AN: 41590

American (AMR) AF: 0.0189 AC: 289 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3472

East Asian (EAS) AF: 0.00541 AC: 28 AN: 5180

South Asian (SAS) AF: 0.0159 AC: 77 AN: 4830

European-Finnish (FIN) AF: 0.0807 AC: 857 AN: 10622

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0297 AC: 2021 AN: 68022

Other (OTH) AF: 0.0208 AC: 44 AN: 2114

Alfa AF: 0.0145 Hom.: 7

Bravo AF: 0.0188

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.8
DANN	Benign	0.74
PhyloP100		0.31
PromoterAI		0.0020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism

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: rs75810419; hg19: chr11-61582527;