11-61829740-C-T

Variant names:

• chr11-61829740-C-T
• rs174570
• NM_004265.4:c.207+1143C>T

Variant summary

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

The NM_004265.4(FADS2):​c.207+1143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,106 control chromosomes in the GnomAD database, including 3,215 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 0.15 (3215 hom., cov: 32)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• Publications: 172 publications found

Genes affected

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FADS2	NM_004265.4	c.207+1143C>T		intron_variant	Intron 1 of 11	ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.142-8038C>T		intron_variant	Intron 1 of 11		NP_001268430.1
FADS2	NM_001281502.1	c.115-8038C>T		intron_variant	Intron 1 of 11		NP_001268431.1
FADS2	XM_047427889.1	c.207+1143C>T		intron_variant	Intron 2 of 12		XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.207+1143C>T		intron_variant	Intron 1 of 11	1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23356 AN: 151988 Hom.: 3193 Cov.: 32

Gnomad AFR AF: 0.0382

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.154 AC: 23394 AN: 152106 Hom.: 3215 Cov.: 32 AF XY: 0.163 AC XY: 12141 AN XY: 74336

African (AFR) AF: 0.0381 AC: 1581 AN: 41550

American (AMR) AF: 0.384 AC: 5857 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 477 AN: 3470

East Asian (EAS) AF: 0.547 AC: 2814 AN: 5144

South Asian (SAS) AF: 0.106 AC: 512 AN: 4820

European-Finnish (FIN) AF: 0.238 AC: 2512 AN: 10564

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9177 AN: 67986

Other (OTH) AF: 0.188 AC: 397 AN: 2112

Alfa AF: 0.142 Hom.: 9449

Bravo AF: 0.165

Asia WGS AF: 0.321 AC: 1114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.1
DANN	Benign	0.83
PhyloP100		-0.45
PromoterAI		-0.021	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: rs174570; hg19: chr11-61597212;