rs174578

Variant names:

• chr11-61838027-T-A
• rs174578
• NM_004265.4:c.318+139T>A

Variant summary

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

The NM_004265.4(FADS2):​c.318+139T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 652,516 control chromosomes in the GnomAD database, including 46,733 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 0.38 (11535 hom., cov: 31)
  • Exomes 𝑓: 0.36 (35198 hom.)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408
• Publications: 73 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 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.318+139T>A		intron	N/A	NP_004256.1	O95864-1
	FADS2	NM_001281501.1		c.252+139T>A		intron	N/A	NP_001268430.1	O95864-2
	FADS2	NM_001281502.1		c.225+139T>A		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.318+139T>A		intron	N/A	ENSP00000278840.4	O95864-1
	FADS2	ENST00000257261.10	TSL:1	c.252+139T>A		intron	N/A	ENSP00000257261.6	O95864-2
	FADS2	ENST00000521849.5	TSL:1	c.318+139T>A		intron	N/A	ENSP00000431091.1	O95864-3

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57287 AN: 151678 Hom.: 11500 Cov.: 31

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.358 AC: 179043 AN: 500720 Hom.: 35198 AF XY: 0.345 AC XY: 91266 AN XY: 264700

African (AFR) AF: 0.374 AC: 5313 AN: 14220

American (AMR) AF: 0.663 AC: 17909 AN: 26998

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 4629 AN: 15388

East Asian (EAS) AF: 0.446 AC: 14044 AN: 31476

South Asian (SAS) AF: 0.179 AC: 9147 AN: 51188

European-Finnish (FIN) AF: 0.427 AC: 13388 AN: 31358

Middle Eastern (MID) AF: 0.297 AC: 649 AN: 2182

European-Non Finnish (NFE) AF: 0.344 AC: 102989 AN: 299812

Other (OTH) AF: 0.391 AC: 10975 AN: 28098

GnomAD4 genome AF: 0.378 AC: 57355 AN: 151796 Hom.: 11535 Cov.: 31 AF XY: 0.380 AC XY: 28206 AN XY: 74166

African (AFR) AF: 0.372 AC: 15379 AN: 41396

American (AMR) AF: 0.533 AC: 8131 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1059 AN: 3466

East Asian (EAS) AF: 0.554 AC: 2843 AN: 5128

South Asian (SAS) AF: 0.183 AC: 881 AN: 4812

European-Finnish (FIN) AF: 0.421 AC: 4438 AN: 10536

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23408 AN: 67880

Other (OTH) AF: 0.407 AC: 861 AN: 2116

Alfa AF: 0.366 Hom.: 1325

Bravo AF: 0.392

Asia WGS AF: 0.395 AC: 1372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.55
PhyloP100		-0.41
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: rs174578; hg19: chr11-61605499;