11-61826344-C-T

Position:

• chr11-61826344-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001281501.1(FADS2):​c.141+9918C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 702,380 control chromosomes in the GnomAD database, including 43,527 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 0.29 (8107 hom., cov: 32)
  • Exomes 𝑓: 0.34 (35420 hom.)
• Consequence: FADS2 NM_001281501.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328

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]

FADS1 (HGNC:3574): (fatty acid desaturase 1) 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 FADS1 and FADS2 at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization. [provided by RefSeq, Jul 2008]

FADS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FADS2	XM_047427889.1	c.-2047C>T		5_prime_UTR_premature_start_codon_gain_variant	2/13		XP_047283845.1
FADS2	XM_047427889.1	c.-2047C>T		5_prime_UTR_variant	2/13		XP_047283845.1
FADS2	NM_001281501.1	c.141+9918C>T		intron_variant			NP_001268430.1
FADS2	NM_001281502.1	c.114+9648C>T		intron_variant			NP_001268431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000257261.10	c.141+9918C>T		intron_variant		1		ENSP00000257261.6
FADS2	ENST00000517839.1	c.*105C>T		3_prime_UTR_variant	3/3	3		ENSP00000429693.1
FADS2	ENST00000522056.5	c.114+9648C>T		intron_variant		2		ENSP00000429500.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43548 AN: 152004 Hom.: 8085 Cov.: 32

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.334

GnomAD3 exomes AF: 0.372 AC: 47785 AN: 128284 Hom.: 11149 AF XY: 0.350 AC XY: 24598 AN XY: 70248

Gnomad AFR exome AF: 0.0698

Gnomad AMR exome AF: 0.650

Gnomad ASJ exome AF: 0.275

Gnomad EAS exome AF: 0.572

Gnomad SAS exome AF: 0.169

Gnomad FIN exome AF: 0.416

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.337 AC: 185357 AN: 550256 Hom.: 35420 Cov.: 0 AF XY: 0.325 AC XY: 96680 AN XY: 297876

Gnomad4 AFR exome AF: 0.0777

Gnomad4 AMR exome AF: 0.632

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.286 AC: 43582 AN: 152124 Hom.: 8107 Cov.: 32 AF XY: 0.293 AC XY: 21750 AN XY: 74348

Gnomad4 AFR AF: 0.0785

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.338

Alfa AF: 0.305 Hom.: 4076

Bravo AF: 0.288

Asia WGS AF: 0.371 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs174568; hg19: chr11-61593816; COSMIC: COSV53898928; COSMIC: COSV53898928;