rs174553

Variant names:

• chr11-61807686-A-G
• rs174553
• NM_013402.7:c.916-962T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-61807686-A-G
• chr11-61807686-A-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.916-962T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,088 control chromosomes in the GnomAD database, including 8,132 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 (8132 hom., cov: 32)
• Consequence: FADS1 NM_013402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 61 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FADS1	NM_013402.7	c.916-962T>C		intron_variant	Intron 5 of 11	ENST00000350997.12	NP_037534.5
FADS1	XM_011545022.3	c.703-962T>C		intron_variant	Intron 5 of 11		XP_011543324.1
FADS1	XM_047426935.1	c.493-962T>C		intron_variant	Intron 5 of 11		XP_047282891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS1	ENST00000350997.12	c.916-962T>C		intron_variant	Intron 5 of 11	1	NM_013402.7	ENSP00000322229.9

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43662 AN: 151970 Hom.: 8110 Cov.: 32

Gnomad AFR AF: 0.0782

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.337

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.287 AC: 43696 AN: 152088 Hom.: 8132 Cov.: 32 AF XY: 0.293 AC XY: 21795 AN XY: 74338

African (AFR) AF: 0.0780 AC: 3241 AN: 41546

American (AMR) AF: 0.487 AC: 7429 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3470

East Asian (EAS) AF: 0.553 AC: 2853 AN: 5158

South Asian (SAS) AF: 0.179 AC: 865 AN: 4824

European-Finnish (FIN) AF: 0.420 AC: 4442 AN: 10564

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

European-Non Finnish (NFE) AF: 0.336 AC: 22844 AN: 67956

Other (OTH) AF: 0.340 AC: 717 AN: 2106

Alfa AF: 0.302 Hom.: 1046

Bravo AF: 0.288

Asia WGS AF: 0.375 AC: 1303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		-0.30
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: rs174553; hg19: chr11-61575158;