chr2-70777360-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001004311.3(FIGLA):c.*7A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,463,918 control chromosomes in the GnomAD database, including 52,927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5391 hom., cov: 32)

Exomes 𝑓: 0.25 ( 47536 hom. )

Consequence

FIGLA
NM_001004311.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.183

Publications

9 publications found

Variant links:

Genes affected

FIGLA (HGNC:24669): (folliculogenesis specific bHLH transcription factor) This gene encodes a protein that functions in postnatal oocyte-specific gene expression. The protein is a basic helix-loop-helix transcription factor that regulates multiple oocyte-specific genes, including genes involved in folliculogenesis and those that encode the zona pellucida. Mutations in this gene cause premature ovarian failure type 6. [provided by RefSeq, Sep 2009]

FIGLA Gene-Disease associations (from GenCC):

premature ovarian failure 6
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

FIGLA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 2-70777360-T-C is Benign according to our data. Variant chr2-70777360-T-C is described in ClinVar as [Benign]. Clinvar id is 197699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGLA	NM_001004311.3 link	c.*7A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000332372.6	NP_001004311.2	Q6QHK4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIGLA	ENST00000332372.6 link	c.*7A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_001004311.3	ENSP00000333097.6		Q6QHK4

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34951

AN:

151648

Hom.:

5397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0616

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.621

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.230

GnomAD2 exomes

AF:

0.279

AC:

38729

AN:

138942

AF XY:

0.281

show subpopulations

Gnomad AFR exome

AF:

0.0508

Gnomad AMR exome

AF:

0.320

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.604

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.243

GnomAD4 exome

AF:

0.249

AC:

326521

AN:

1312188

Hom.:

47536

Cov.:

AF XY:

0.252

AC XY:

163710

AN XY:

648604

show subpopulations

African (AFR)

AF:

0.0484

AC:

1436

AN:

29672

American (AMR)

AF:

0.333

AC:

8529

AN:

25598

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

3781

AN:

23552

East Asian (EAS)

AF:

0.675

AC:

23690

AN:

35072

South Asian (SAS)

AF:

0.344

AC:

22970

AN:

66694

European-Finnish (FIN)

AF:

0.378

AC:

18314

AN:

48402

Middle Eastern (MID)

AF:

0.224

AC:

1208

AN:

5386

European-Non Finnish (NFE)

AF:

0.228

AC:

233137

AN:

1023412

Other (OTH)

AF:

0.247

AC:

13456

AN:

54400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

9149

18299

27448

36598

45747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.230

AC:

34945

AN:

151730

Hom.:

5391

Cov.:

AF XY:

0.243

AC XY:

18023

AN XY:

74074

show subpopulations

African (AFR)

AF:

0.0614

AC:

2545

AN:

41446

American (AMR)

AF:

0.323

AC:

4919

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

607

AN:

3468

East Asian (EAS)

AF:

0.621

AC:

3197

AN:

5148

South Asian (SAS)

AF:

0.397

AC:

1907

AN:

4804

European-Finnish (FIN)

AF:

0.385

AC:

3999

AN:

10396

Middle Eastern (MID)

AF:

0.205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.250

AC:

16983

AN:

67928

Other (OTH)

AF:

0.228

AC:

481

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1205

2410

3614

4819

6024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.220

Hom.:

1876

Bravo

AF:

0.218

Asia WGS

AF:

0.466

AC:

1620

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Premature ovarian failure 6

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Nov 15, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

FIGLA-related condition

Benign:1

Jun 21, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

-0.18

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr2-70777360-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over