Genetic Variant NM_001004311.3:c.610-175G>A (chr2-70777846-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001004311.3(FIGLA):c.610-175G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 152,236 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 13 hom., cov: 33)

Consequence

FIGLA
NM_001004311.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.416

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-70777846-C-T is Benign according to our data. Variant chr2-70777846-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1223176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0117 (1778/152236) while in subpopulation NFE AF = 0.0177 (1207/68022). AF 95% confidence interval is 0.0169. There are 13 homozygotes in GnomAd4. There are 874 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1778 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGLA	NM_001004311.3 link	c.610-175G>A		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.610-175G>A		intron_variant	Intron 3 of 4	1	NM_001004311.3	ENSP00000333097.6		Q6QHK4

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1777

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00353

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00788

Gnomad FIN

AF:

0.00575

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0177

Gnomad OTH

AF:

0.0144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0117

AC:

1778

AN:

152236

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

874

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00354

AC:

147

AN:

41534

American (AMR)

AF:

0.0144

AC:

220

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00788

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00575

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0177

AC:

1207

AN:

68022

Other (OTH)

AF:

0.0142

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

103

206

309

412

515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.68

(source)

DANN

Benign

0.18

PhyloP100

-0.42

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

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NM_001004311.3:c.610-175G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over