Genetic Variant NM_001004311.3:c.609+148T>G (chr2-70785267-A-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001004311.3(FIGLA):c.609+148T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 712,116 control chromosomes in the GnomAD database, including 12,170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3183 hom., cov: 32)

Exomes 𝑓: 0.17 ( 8987 hom. )

Consequence

FIGLA
NM_001004311.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0710

Publications

1 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-70785267-A-C is Benign according to our data. Variant chr2-70785267-A-C is described in ClinVar as [Benign]. Clinvar id is 1276509.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGLA	NM_001004311.3 link	c.609+148T>G		intron_variant	Intron 3 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.609+148T>G		intron_variant	Intron 3 of 4	1	NM_001004311.3	ENSP00000333097.6		Q6QHK4

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30253

AN:

152014

Hom.:

3176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.233

GnomAD4 exome

AF:

0.173

AC:

97098

AN:

559984

Hom.:

8987

AF XY:

0.173

AC XY:

50107

AN XY:

289718

show subpopulations

African (AFR)

AF:

0.258

AC:

3724

AN:

14408

American (AMR)

AF:

0.138

AC:

2634

AN:

19106

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

4301

AN:

14294

East Asian (EAS)

AF:

0.112

AC:

3633

AN:

32454

South Asian (SAS)

AF:

0.164

AC:

7007

AN:

42828

European-Finnish (FIN)

AF:

0.187

AC:

6846

AN:

36594

Middle Eastern (MID)

AF:

0.273

AC:

595

AN:

2182

European-Non Finnish (NFE)

AF:

0.170

AC:

62679

AN:

368680

Other (OTH)

AF:

0.193

AC:

5679

AN:

29438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

3836

7672

11507

15343

19179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.199

AC:

30297

AN:

152132

Hom.:

3183

Cov.:

AF XY:

0.200

AC XY:

14852

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.247

AC:

10256

AN:

41496

American (AMR)

AF:

0.174

AC:

2663

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

1080

AN:

3462

East Asian (EAS)

AF:

0.114

AC:

592

AN:

5188

South Asian (SAS)

AF:

0.162

AC:

780

AN:

4818

European-Finnish (FIN)

AF:

0.201

AC:

2127

AN:

10592

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.177

AC:

12027

AN:

67978

Other (OTH)

AF:

0.239

AC:

504

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1232

2464

3697

4929

6161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.160

Hom.:

802

Bravo

AF:

0.202

Asia WGS

AF:

0.169

AC:

587

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.0

(source)

DANN

Benign

0.77

PhyloP100

-0.071

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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NM_001004311.3:c.609+148T>G

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