chr2-70777362-A-T

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.*5T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,465,808 control chromosomes in the GnomAD database, including 53,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5393 hom., cov: 32)

Exomes 𝑓: 0.25 ( 47789 hom. )

Consequence

FIGLA
NM_001004311.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.970

Publications

7 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=-0.65).

BP6

Variant 2-70777362-A-T is Benign according to our data. Variant chr2-70777362-A-T is described in ClinVar as [Benign]. Clinvar id is 197698.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.*5T>A		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.*5T>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_001004311.3	ENSP00000333097.6		Q6QHK4

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

34961

AN:

151586

Hom.:

5399

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0617

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:

38701

AN:

138808

AF XY:

0.281

show subpopulations

Gnomad AFR exome

AF:

0.0503

Gnomad AMR exome

AF:

0.321

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.603

Gnomad FIN exome

AF:

0.373

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.243

GnomAD4 exome

AF:

0.249

AC:

327867

AN:

1314108

Hom.:

47789

Cov.:

AF XY:

0.253

AC XY:

164306

AN XY:

649406

show subpopulations

African (AFR)

AF:

0.0484

AC:

1434

AN:

29644

American (AMR)

AF:

0.334

AC:

8537

AN:

25564

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

3784

AN:

23554

East Asian (EAS)

AF:

0.675

AC:

23690

AN:

35084

South Asian (SAS)

AF:

0.345

AC:

23010

AN:

66686

European-Finnish (FIN)

AF:

0.378

AC:

18308

AN:

48386

Middle Eastern (MID)

AF:

0.225

AC:

1213

AN:

5386

European-Non Finnish (NFE)

AF:

0.229

AC:

234392

AN:

1025368

Other (OTH)

AF:

0.248

AC:

13499

AN:

54436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

9226

18452

27677

36903

46129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.230

AC:

34955

AN:

151700

Hom.:

5393

Cov.:

AF XY:

0.243

AC XY:

18027

AN XY:

74088

show subpopulations

African (AFR)

AF:

0.0615

AC:

2547

AN:

41442

American (AMR)

AF:

0.323

AC:

4921

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

607

AN:

3468

East Asian (EAS)

AF:

0.621

AC:

3198

AN:

5148

South Asian (SAS)

AF:

0.396

AC:

1906

AN:

4812

European-Finnish (FIN)

AF:

0.385

AC:

4005

AN:

10392

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.250

AC:

16983

AN:

67900

Other (OTH)

AF:

0.228

AC:

481

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1188

2376

3563

4751

5939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.230

Hom.:

1501

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

-0.65

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

0.97

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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chr2-70777362-A-T

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