Genetic Variant NM_021727.5:c.213+715T>C (chr11-61890454-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_021727.5(FADS3):c.213+715T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,280 control chromosomes in the GnomAD database, including 30,060 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 0.59 ( 29994 hom., cov: 32)

Exomes 𝑓: 0.73 ( 66 hom. )

Consequence

FADS3
NM_021727.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.412

Publications

12 publications found

Variant links:

Genes affected

FADS3 (HGNC:3576): (fatty acid desaturase 3) 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]

FADS3 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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021727.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS3	NM_021727.5	MANE Select	c.213+715T>C		intron	N/A	NP_068373.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FADS3	ENST00000278829.7	TSL:1 MANE Select	c.213+715T>C	intron	N/A	ENSP00000278829.2
FADS3	ENST00000969795.1		c.213+715T>C	intron	N/A	ENSP00000639854.1
FADS3	ENST00000969794.1		c.213+715T>C	intron	N/A	ENSP00000639853.1

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90374

AN:

151928

Hom.:

29996

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.811

Gnomad AMR

AF:

0.516

Gnomad ASJ

AF:

0.760

Gnomad EAS

AF:

0.679

Gnomad SAS

AF:

0.629

Gnomad FIN

AF:

0.775

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.746

Gnomad OTH

AF:

0.610

GnomAD4 exome

AF:

0.726

AC:

170

AN:

234

Hom.:

AF XY:

0.726

AC XY:

138

AN XY:

190

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.167

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.591

AC:

AN:

European-Finnish (FIN)

AF:

0.625

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.759

AC:

132

AN:

174

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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:

0.594

AC:

90370

AN:

152046

Hom.:

29994

Cov.:

AF XY:

0.596

AC XY:

44296

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.295

AC:

12217

AN:

41456

American (AMR)

AF:

0.515

AC:

7875

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.760

AC:

2637

AN:

3470

East Asian (EAS)

AF:

0.679

AC:

3504

AN:

5158

South Asian (SAS)

AF:

0.629

AC:

3032

AN:

4820

European-Finnish (FIN)

AF:

0.775

AC:

8209

AN:

10592

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.746

AC:

50699

AN:

67954

Other (OTH)

AF:

0.608

AC:

1283

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1595

3190

4786

6381

7976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

738

1476

2214

2952

3690

<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:

0.647

Hom.:

5030

Bravo

AF:

0.560

Asia WGS

AF:

0.608

AC:

2115

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.0

(source)

DANN

Benign

0.54

PhyloP100

-0.41

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over