Genetic Variant NM_001004311.3:c.644+109_644+112delGGAA (chr2-70777524-ATTCC-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001004311.3(FIGLA):c.644+109_644+112delGGAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,471,222 control chromosomes in the GnomAD database, including 382 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.016 ( 33 hom., cov: 32)

Exomes 𝑓: 0.022 ( 349 hom. )

Consequence

FIGLA
NM_001004311.3 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0880

Publications

0 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 -10 ACMG points.

BP6

Variant 2-70777524-ATTCC-A is Benign according to our data. Variant chr2-70777524-ATTCC-A is described in ClinVar as [Likely_benign]. Clinvar id is 1207553.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0165 (2509/152306) while in subpopulation NFE AF = 0.0221 (1503/68028). AF 95% confidence interval is 0.0212. There are 33 homozygotes in GnomAd4. There are 1322 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2509 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGLA	NM_001004311.3 link	c.644+109_644+112delGGAA		intron_variant	Intron 4 of 4	ENST00000332372.6	NP_001004311.2	Q6QHK4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIGLA	ENST00000332372.6 link	c.644+109_644+112delGGAA		intron_variant	Intron 4 of 4	1	NM_001004311.3	ENSP00000333097.6		Q6QHK4

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2508

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00413

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0154

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.0367

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0221

Gnomad OTH

AF:

0.0172

GnomAD4 exome

AF:

0.0219

AC:

28894

AN:

1318916

Hom.:

349

AF XY:

0.0220

AC XY:

14315

AN XY:

650130

show subpopulations

African (AFR)

AF:

0.00292

AC:

AN:

29790

American (AMR)

AF:

0.0121

AC:

377

AN:

31206

Ashkenazi Jewish (ASJ)

AF:

0.0227

AC:

548

AN:

24146

East Asian (EAS)

AF:

0.000490

AC:

AN:

34714

South Asian (SAS)

AF:

0.0201

AC:

1404

AN:

69996

European-Finnish (FIN)

AF:

0.0317

AC:

1541

AN:

48676

Middle Eastern (MID)

AF:

0.0271

AC:

149

AN:

5502

European-Non Finnish (NFE)

AF:

0.0232

AC:

23625

AN:

1019684

Other (OTH)

AF:

0.0208

AC:

1146

AN:

55202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1344

2688

4031

5375

6719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0165

AC:

2509

AN:

152306

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1322

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00414

AC:

172

AN:

41572

American (AMR)

AF:

0.0154

AC:

235

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3472

East Asian (EAS)

AF:

0.000964

AC:

AN:

5188

South Asian (SAS)

AF:

0.0154

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0367

AC:

389

AN:

10604

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0221

AC:

1503

AN:

68028

Other (OTH)

AF:

0.0170

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

128

255

383

510

638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0168

Hom.:

Bravo

AF:

0.0139

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 25, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.088

Mutation Taster

=100/0

polymorphism

(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.

NM_001004311.3:c.644+109_644+112delGGAA

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