NM_004265.4:c.618+1553C>T

Variant names:

• chr11-61842278-C-T
• rs174583
• NM_004265.4:c.618+1553C>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.618+1553C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,194 control chromosomes in the GnomAD database, including 10,272 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 0.35 (10272 hom., cov: 33)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34
• Publications: 167 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=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004265.4. 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
	FADS2	NM_004265.4	MANE Select	c.618+1553C>T		intron	N/A	NP_004256.1	O95864-1
	FADS2	NM_001281501.1		c.552+1553C>T		intron	N/A	NP_001268430.1	O95864-2
	FADS2	NM_001281502.1		c.525+1553C>T		intron	N/A	NP_001268431.1	O95864-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS2	ENST00000278840.9	TSL:1 MANE Select	c.618+1553C>T		intron	N/A	ENSP00000278840.4	O95864-1
	FADS2	ENST00000257261.10	TSL:1	c.552+1553C>T		intron	N/A	ENSP00000257261.6	O95864-2
	FADS2	ENST00000521849.5	TSL:1	c.618+1553C>T		intron	N/A	ENSP00000431091.1	O95864-3

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53601 AN: 152076 Hom.: 10239 Cov.: 33

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.353 AC: 53677 AN: 152194 Hom.: 10272 Cov.: 33 AF XY: 0.357 AC XY: 26558 AN XY: 74408

African (AFR) AF: 0.278 AC: 11561 AN: 41542

American (AMR) AF: 0.523 AC: 7987 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1076 AN: 3472

East Asian (EAS) AF: 0.555 AC: 2870 AN: 5172

South Asian (SAS) AF: 0.201 AC: 970 AN: 4830

European-Finnish (FIN) AF: 0.421 AC: 4461 AN: 10584

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23571 AN: 67998

Other (OTH) AF: 0.390 AC: 824 AN: 2112

Alfa AF: 0.353 Hom.: 37307

Bravo AF: 0.361

Asia WGS AF: 0.403 AC: 1399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.29
DANN	Benign	0.90
PhyloP100		-3.3
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: rs174583; hg19: chr11-61609750;