chr11-61827448-CT-C

Position:

• chr11-61827448-CT-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001281501.1(FADS2):​c.142-10329delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,130 control chromosomes in the GnomAD database, including 8,063 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (8053 hom., cov: 22)
  • Exomes 𝑓: 0.37 (10 hom.)
• Consequence: FADS2 NM_001281501.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FADS2	XM_047427889.1	c.-942delT		5_prime_UTR_variant	2/13		XP_047283845.1
FADS2	NM_001281501.1	c.142-10329delT		intron_variant			NP_001268430.1
FADS2	NM_001281502.1	c.115-10329delT		intron_variant			NP_001268431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000257261.10	c.142-10329delT		intron_variant		1		ENSP00000257261.6
FADS2	ENST00000522056.5	c.115-10329delT		intron_variant		2		ENSP00000429500.1
FADS1	ENST00000421879.5	c.-49+1752delA		intron_variant		3		ENSP00000416043.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43439 AN: 151888 Hom.: 8031 Cov.: 22

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.371 AC: 46 AN: 124 Hom.: 10 Cov.: 0 AF XY: 0.385 AC XY: 20 AN XY: 52

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.286 AC: 43473 AN: 152006 Hom.: 8053 Cov.: 22 AF XY: 0.292 AC XY: 21676 AN XY: 74302

Gnomad4 AFR AF: 0.0781

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.338

Alfa AF: 0.180 Hom.: 411

Bravo AF: 0.288

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3834458; hg19: chr11-61594920;