chr11-61855668-C-T

Position:

• chr11-61855668-C-T

Variant summary

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

The NM_004265.4(FADS2):​c.745-1343C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,134 control chromosomes in the GnomAD database, including 17,573 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 0.46 (17566 hom., cov: 33)
  • Exomes 𝑓: 0.36 (7 hom.)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FADS2	NM_004265.4	c.745-1343C>T		intron_variant		ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.679-1343C>T		intron_variant			NP_001268430.1
FADS2	NM_001281502.1	c.652-1343C>T		intron_variant			NP_001268431.1
FADS2	XM_047427889.1	c.745-1343C>T		intron_variant			XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.745-1343C>T		intron_variant		1	NM_004265.4	ENSP00000278840	P1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70259 AN: 151946 Hom.: 17526 Cov.: 33

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.469

GnomAD4 exome AF: 0.357 AC: 25 AN: 70 Hom.: 7 Cov.: 0 AF XY: 0.396 AC XY: 19 AN XY: 48

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.328

GnomAD4 genome AF: 0.463 AC: 70353 AN: 152064 Hom.: 17566 Cov.: 33 AF XY: 0.463 AC XY: 34400 AN XY: 74318

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.471

Alfa AF: 0.358 Hom.: 9504

Bravo AF: 0.484

Asia WGS AF: 0.449 AC: 1561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs174601; hg19: chr11-61623140;