Genetic Variant FOXL2NB:c.100+616T>C (chr3-138948080-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001040061.3(FOXL2NB):c.100+616T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 681,452 control chromosomes in the GnomAD database, including 4,234 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 0.14 ( 2932 hom., cov: 32)

Exomes 𝑓: 0.048 ( 1302 hom. )

Consequence

FOXL2NB
NM_001040061.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.605

Publications

3 publications found

Variant links:

Genes affected

FOXL2NB (HGNC:34428): (FOXL2 neighbor) Located in fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

FOXL2NB links:

Genome browser will be placed here

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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXL2NB	NM_001040061.3 link	c.100+616T>C		intron_variant	Intron 1 of 2	ENST00000383165.4	NP_001035150.1	Q6ZUU3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXL2NB	ENST00000383165.4 link	c.100+616T>C	intron_variant	Intron 1 of 2	2	NM_001040061.3	ENSP00000372651.3	Q6ZUU3
FOXL2NB	ENST00000470680.5 link	n.100+616T>C	intron_variant	Intron 1 of 2	3		ENSP00000418272.1	F8WBY5
FOXL2NB	ENST00000498709.1 link	n.396+73T>C	intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21296

AN:

152102

Hom.:

2920

Cov.:

show subpopulations

Gnomad AFR

AF:

0.362

Gnomad AMI

AF:

0.0910

Gnomad AMR

AF:

0.0626

Gnomad ASJ

AF:

0.0536

Gnomad EAS

AF:

0.0329

Gnomad SAS

AF:

0.0728

Gnomad FIN

AF:

0.0960

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0485

Gnomad OTH

AF:

0.109

GnomAD4 exome

AF:

0.0482

AC:

25508

AN:

529232

Hom.:

1302

AF XY:

0.0485

AC XY:

12013

AN XY:

247820

show subpopulations

African (AFR)

AF:

0.394

AC:

3787

AN:

9610

American (AMR)

AF:

0.0403

AC:

AN:

620

Ashkenazi Jewish (ASJ)

AF:

0.0474

AC:

154

AN:

3250

East Asian (EAS)

AF:

0.0177

AC:

AN:

2198

South Asian (SAS)

AF:

0.0736

AC:

756

AN:

10278

European-Finnish (FIN)

AF:

0.0753

AC:

AN:

186

Middle Eastern (MID)

AF:

0.0733

AC:

AN:

1010

European-Non Finnish (NFE)

AF:

0.0404

AC:

19573

AN:

484774

Other (OTH)

AF:

0.0628

AC:

1086

AN:

17306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1093

2186

3280

4373

5466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1098

2196

3294

4392

5490

<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:

0.140

AC:

21363

AN:

152220

Hom.:

2932

Cov.:

AF XY:

0.139

AC XY:

10324

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.363

AC:

15036

AN:

41466

American (AMR)

AF:

0.0625

AC:

956

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0536

AC:

186

AN:

3470

East Asian (EAS)

AF:

0.0330

AC:

171

AN:

5188

South Asian (SAS)

AF:

0.0727

AC:

351

AN:

4828

European-Finnish (FIN)

AF:

0.0960

AC:

1020

AN:

10620

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0485

AC:

3300

AN:

68022

Other (OTH)

AF:

0.114

AC:

241

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

806

1612

2419

3225

4031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

204

408

612

816

1020

<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:

0.0626

Hom.:

1121

Bravo

AF:

0.145

Asia WGS

AF:

0.0820

AC:

288

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.5

(source)

DANN

Benign

0.58

PhyloP100

0.60

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