2-70777360-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.183

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
FIGLA	NM_001004311.3	c.*7A>G		3_prime_UTR_variant	5/5	ENST00000332372.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FIGLA	ENST00000332372.6	c.*7A>G		3_prime_UTR_variant	5/5	1	NM_001004311.3	P1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34951 AN: 151648 Hom.: 5397 Cov.: 32

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

GnomAD3 exomes AF: 0.279 AC: 38729 AN: 138942 Hom.: 6686 AF XY: 0.281 AC XY: 20841 AN XY: 74202

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 SAS exome AF: 0.346

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.: 25 AF XY: 0.252 AC XY: 163710 AN XY: 648604

Gnomad4 AFR exome AF: 0.0484

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.675

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.230 AC: 34945 AN: 151730 Hom.: 5391 Cov.: 32 AF XY: 0.243 AC XY: 18023 AN XY: 74074

Gnomad4 AFR AF: 0.0614

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.228

Alfa AF: 0.221 Hom.: 1871

Bravo AF: 0.218

Asia WGS AF: 0.466 AC: 1620 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Premature ovarian failure 6 Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Nov 15, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	11
Dann	Benign	0.90

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

LitVar

Other links and lift over

dbSNP: rs56316086; hg19: chr2-71004492;