Genetic Variant NM_004265.4:c.806-41G>C (chr11-61857413-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004265.4(FADS2):c.806-41G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 1,576,556 control chromosomes in the GnomAD database, including 515,138 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 0.69 ( 40007 hom., cov: 32)

Exomes 𝑓: 0.81 ( 475131 hom. )

Consequence

FADS2
NM_004265.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.361

Variant links:

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]

FADS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FADS2	NM_004265.4 link	c.806-41G>C	intron_variant	Intron 6 of 11	ENST00000278840.9	NP_004256.1	O95864-1
FADS2	NM_001281501.1 link	c.740-41G>C	intron_variant	Intron 6 of 11		NP_001268430.1	O95864-2
FADS2	NM_001281502.1 link	c.713-41G>C	intron_variant	Intron 6 of 11		NP_001268431.1	O95864-4
FADS2	XM_047427889.1 link	c.806-41G>C	intron_variant	Intron 7 of 12		XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9 link	c.806-41G>C		intron_variant	Intron 6 of 11	1	NM_004265.4	ENSP00000278840.4		O95864-1

Frequencies

GnomAD3 genomes

AF:

0.689

AC:

104794

AN:

151998

Hom.:

39987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.742

Gnomad AMR

AF:

0.814

Gnomad ASJ

AF:

0.783

Gnomad EAS

AF:

0.839

Gnomad SAS

AF:

0.885

Gnomad FIN

AF:

0.891

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.817

Gnomad OTH

AF:

0.712

GnomAD3 exomes

AF:

0.810

AC:

202408

AN:

250024

Hom.:

84315

AF XY:

0.820

AC XY:

110930

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.319

Gnomad AMR exome

AF:

0.879

Gnomad ASJ exome

AF:

0.798

Gnomad EAS exome

AF:

0.825

Gnomad SAS exome

AF:

0.885

Gnomad FIN exome

AF:

0.888

Gnomad NFE exome

AF:

0.822

Gnomad OTH exome

AF:

0.820

GnomAD4 exome

AF:

0.812

AC:

1156607

AN:

1424440

Hom.:

475131

Cov.:

AF XY:

0.816

AC XY:

580201

AN XY:

711184

show subpopulations

Gnomad4 AFR exome

AF:

0.309

Gnomad4 AMR exome

AF:

0.872

Gnomad4 ASJ exome

AF:

0.796

Gnomad4 EAS exome

AF:

0.875

Gnomad4 SAS exome

AF:

0.888

Gnomad4 FIN exome

AF:

0.889

Gnomad4 NFE exome

AF:

0.815

Gnomad4 OTH exome

AF:

0.781

GnomAD4 genome

AF:

0.689

AC:

104849

AN:

152116

Hom.:

40007

Cov.:

AF XY:

0.701

AC XY:

52113

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.330

Gnomad4 AMR

AF:

0.815

Gnomad4 ASJ

AF:

0.783

Gnomad4 EAS

AF:

0.839

Gnomad4 SAS

AF:

0.884

Gnomad4 FIN

AF:

0.891

Gnomad4 NFE

AF:

0.817

Gnomad4 OTH

AF:

0.714

Alfa

AF:

0.734

Hom.:

5324

Bravo

AF:

0.669

Asia WGS

AF:

0.823

AC:

2862

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.2

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over