Genetic Variant FADS2:c.745-1343C>T (chr11-61855668-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.49

Publications

93 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein
FADS2	NM_004265.4 link	c.745-1343C>T	intron_variant	Intron 5 of 11	ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1 link	c.679-1343C>T	intron_variant	Intron 5 of 11		NP_001268430.1
FADS2	NM_001281502.1 link	c.652-1343C>T	intron_variant	Intron 5 of 11		NP_001268431.1
FADS2	XM_047427889.1 link	c.745-1343C>T	intron_variant	Intron 6 of 12		XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9 link	c.745-1343C>T		intron_variant	Intron 5 of 11	1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes

AF:

0.462

AC:

70259

AN:

151946

Hom.:

17526

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.396

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.328

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.463

AC:

70353

AN:

152064

Hom.:

17566

Cov.:

AF XY:

0.463

AC XY:

34400

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.611

AC:

25342

AN:

41504

American (AMR)

AF:

0.565

AC:

8640

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.335

AC:

1163

AN:

3472

East Asian (EAS)

AF:

0.568

AC:

2927

AN:

5150

South Asian (SAS)

AF:

0.255

AC:

1232

AN:

4828

European-Finnish (FIN)

AF:

0.429

AC:

4533

AN:

10560

Middle Eastern (MID)

AF:

0.459

AC:

134

AN:

292

European-Non Finnish (NFE)

AF:

0.369

AC:

25053

AN:

67944

Other (OTH)

AF:

0.471

AC:

995

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1807

3614

5421

7228

9035

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

614

1228

1842

2456

3070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.392

Hom.:

34109

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

(source)

DANN

Benign

0.46

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over