NM_004265.4:c.207+4273A>C

Variant names:

• chr11-61832870-A-C
• rs174574
• NM_004265.4:c.207+4273A>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.207+4273A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,168 control chromosomes in the GnomAD database, including 24,954 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 0.55 (24954 hom., cov: 33)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282
• Publications: 103 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.795 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.207+4273A>C		intron	N/A	NP_004256.1
	FADS2	NM_001281501.1		c.142-4908A>C		intron	N/A	NP_001268430.1
	FADS2	NM_001281502.1		c.115-4908A>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.207+4273A>C		intron	N/A	ENSP00000278840.4
	FADS2	ENST00000257261.10	TSL:1	c.142-4908A>C		intron	N/A	ENSP00000257261.6
	FADS2	ENST00000521849.5	TSL:1	c.207+4273A>C		intron	N/A	ENSP00000431091.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84340 AN: 152050 Hom.: 24955 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.554 AC: 84348 AN: 152168 Hom.: 24954 Cov.: 33 AF XY: 0.553 AC XY: 41182 AN XY: 74408

African (AFR) AF: 0.392 AC: 16276 AN: 41494

American (AMR) AF: 0.439 AC: 6717 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2417 AN: 3472

East Asian (EAS) AF: 0.445 AC: 2306 AN: 5180

South Asian (SAS) AF: 0.817 AC: 3940 AN: 4824

European-Finnish (FIN) AF: 0.579 AC: 6133 AN: 10598

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44559 AN: 67996

Other (OTH) AF: 0.545 AC: 1151 AN: 2112

Alfa AF: 0.621 Hom.: 73070

Bravo AF: 0.532

Asia WGS AF: 0.589 AC: 2051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.90
DANN	Benign	0.66
PhyloP100		-0.28
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: rs174574; hg19: chr11-61600342;