rs174572

Variant names:

• chr11-61830816-C-T
• rs174572
• NM_004265.4:c.207+2219C>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+2219C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,166 control chromosomes in the GnomAD database, including 3,488 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 0.19 (3488 hom., cov: 32)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740
• Publications: 21 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FADS2	NM_004265.4	c.207+2219C>T		intron_variant	Intron 1 of 11	ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.142-6962C>T		intron_variant	Intron 1 of 11		NP_001268430.1
FADS2	NM_001281502.1	c.115-6962C>T		intron_variant	Intron 1 of 11		NP_001268431.1
FADS2	XM_047427889.1	c.207+2219C>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+2219C>T		intron_variant	Intron 1 of 11	1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29126 AN: 152046 Hom.: 3489 Cov.: 32

Gnomad AFR AF: 0.0574

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.191 AC: 29130 AN: 152166 Hom.: 3488 Cov.: 32 AF XY: 0.190 AC XY: 14117 AN XY: 74386

African (AFR) AF: 0.0572 AC: 2377 AN: 41542

American (AMR) AF: 0.287 AC: 4386 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3470

East Asian (EAS) AF: 0.154 AC: 800 AN: 5182

South Asian (SAS) AF: 0.121 AC: 584 AN: 4824

European-Finnish (FIN) AF: 0.222 AC: 2352 AN: 10574

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17129 AN: 67972

Other (OTH) AF: 0.226 AC: 476 AN: 2108

Alfa AF: 0.143 Hom.: 550

Bravo AF: 0.191

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.85
DANN	Benign	0.50
PhyloP100		-0.74
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: rs174572; hg19: chr11-61598288;