11-61845358-C-T

Variant names:

• chr11-61845358-C-T
• rs174587
• NM_004265.4:c.619-2801C>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.619-2801C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,178 control chromosomes in the GnomAD database, including 2,323 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 0.15 (2323 hom., cov: 30)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 11 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FADS2	NM_004265.4	c.619-2801C>T		intron_variant	Intron 4 of 11	ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.553-2801C>T		intron_variant	Intron 4 of 11		NP_001268430.1
FADS2	NM_001281502.1	c.526-2801C>T		intron_variant	Intron 4 of 11		NP_001268431.1
FADS2	XM_047427889.1	c.619-2801C>T		intron_variant	Intron 5 of 12		XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.619-2801C>T		intron_variant	Intron 4 of 11	1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23302 AN: 152060 Hom.: 2326 Cov.: 30

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.153 AC: 23297 AN: 152178 Hom.: 2323 Cov.: 30 AF XY: 0.150 AC XY: 11175 AN XY: 74398

African (AFR) AF: 0.0453 AC: 1883 AN: 41534

American (AMR) AF: 0.257 AC: 3930 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3472

East Asian (EAS) AF: 0.141 AC: 731 AN: 5170

South Asian (SAS) AF: 0.103 AC: 499 AN: 4828

European-Finnish (FIN) AF: 0.130 AC: 1372 AN: 10590

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13797 AN: 67992

Other (OTH) AF: 0.182 AC: 383 AN: 2108

Alfa AF: 0.0863 Hom.: 115

Bravo AF: 0.159

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		-1.4
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: rs174587; hg19: chr11-61612830;