rs174602

Variant names:

• chr11-61856942-T-C
• rs174602
• NM_004265.4:c.745-69T>C

Variant summary

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

The NM_004265.4(FADS2):​c.745-69T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,204,716 control chromosomes in the GnomAD database, including 49,681 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 0.36 (13305 hom., cov: 32)
  • Exomes 𝑓: 0.24 (36376 hom.)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.21
• Publications: 59 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS2	NM_004265.4	MANE Select	c.745-69T>C		intron	N/A	NP_004256.1
	FADS2	NM_001281501.1		c.679-69T>C		intron	N/A	NP_001268430.1
	FADS2	NM_001281502.1		c.652-69T>C		intron	N/A	NP_001268431.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS2	ENST00000278840.9	TSL:1 MANE Select	c.745-69T>C		intron	N/A	ENSP00000278840.4
	FADS2	ENST00000257261.10	TSL:1	c.679-69T>C		intron	N/A	ENSP00000257261.6
	FADS2	ENST00000521849.5	TSL:1	c.745-69T>C		intron	N/A	ENSP00000431091.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55036 AN: 151822 Hom.: 13257 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.239 AC: 251115 AN: 1052776 Hom.: 36376 Cov.: 15 AF XY: 0.234 AC XY: 126904 AN XY: 542816

African (AFR) AF: 0.688 AC: 17609 AN: 25588

American (AMR) AF: 0.539 AC: 23782 AN: 44144

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 4960 AN: 23502

East Asian (EAS) AF: 0.301 AC: 11383 AN: 37822

South Asian (SAS) AF: 0.214 AC: 16692 AN: 77994

European-Finnish (FIN) AF: 0.209 AC: 11062 AN: 53048

Middle Eastern (MID) AF: 0.249 AC: 1230 AN: 4944

European-Non Finnish (NFE) AF: 0.205 AC: 151394 AN: 738718

Other (OTH) AF: 0.277 AC: 13003 AN: 47016

GnomAD4 genome AF: 0.363 AC: 55143 AN: 151940 Hom.: 13305 Cov.: 32 AF XY: 0.361 AC XY: 26798 AN XY: 74288

African (AFR) AF: 0.675 AC: 27974 AN: 41440

American (AMR) AF: 0.431 AC: 6583 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 723 AN: 3466

East Asian (EAS) AF: 0.360 AC: 1853 AN: 5150

South Asian (SAS) AF: 0.218 AC: 1048 AN: 4812

European-Finnish (FIN) AF: 0.208 AC: 2200 AN: 10574

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13754 AN: 67918

Other (OTH) AF: 0.351 AC: 742 AN: 2112

Alfa AF: 0.265 Hom.: 10155

Bravo AF: 0.396

Asia WGS AF: 0.348 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.013
DANN	Benign	0.44
PhyloP100		-5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs174602; hg19: chr11-61624414; COSMIC: COSV53903306;