dbSNP rs2072114: FADS2:c.208-35A>G (chr11-61837743-A-G) – 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.208-35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,443,444 control chromosomes in the GnomAD database, including 18,227 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 0.16 ( 2422 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15805 hom. )

Consequence

FADS2
NM_004265.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.465

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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FADS2	NM_004265.4 link	c.208-35A>G	intron_variant	Intron 1 of 11	ENST00000278840.9	NP_004256.1	O95864-1
FADS2	NM_001281501.1 link	c.142-35A>G	intron_variant	Intron 1 of 11		NP_001268430.1	O95864-2
FADS2	NM_001281502.1 link	c.115-35A>G	intron_variant	Intron 1 of 11		NP_001268431.1	O95864-4
FADS2	XM_047427889.1 link	c.208-35A>G	intron_variant	Intron 2 of 12		XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9 link	c.208-35A>G		intron_variant	Intron 1 of 11	1	NM_004265.4	ENSP00000278840.4		O95864-1

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24292

AN:

152118

Hom.:

2411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.411

Gnomad SAS

AF:

0.0757

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.166

GnomAD3 exomes

AF:

0.185

AC:

35826

AN:

193362

Hom.:

4567

AF XY:

0.173

AC XY:

17936

AN XY:

103438

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.323

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.428

Gnomad SAS exome

AF:

0.0676

Gnomad FIN exome

AF:

0.281

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.173

GnomAD4 exome

AF:

0.142

AC:

182936

AN:

1291208

Hom.:

15805

Cov.:

AF XY:

0.139

AC XY:

89512

AN XY:

646162

show subpopulations

Gnomad4 AFR exome

AF:

0.127

Gnomad4 AMR exome

AF:

0.312

Gnomad4 ASJ exome

AF:

0.122

Gnomad4 EAS exome

AF:

0.345

Gnomad4 SAS exome

AF:

0.0685

Gnomad4 FIN exome

AF:

0.285

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.160

AC:

24347

AN:

152236

Hom.:

2422

Cov.:

AF XY:

0.168

AC XY:

12494

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.239

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.411

Gnomad4 SAS

AF:

0.0764

Gnomad4 FIN

AF:

0.286

Gnomad4 NFE

AF:

0.131

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.135

Hom.:

1497

Bravo

AF:

0.160

Asia WGS

AF:

0.236

AC:

818

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.12

DANN

Benign

0.30

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

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