2-70777362-A-T

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.*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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.970

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=-0.65).
• 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/exons	MANE	UniProt
FIGLA	NM_001004311.3	c.*5T>A		3_prime_UTR_variant	5/5	ENST00000332372.6

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.231 AC: 34961 AN: 151586 Hom.: 5399 Cov.: 32

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

GnomAD3 exomes AF: 0.279 AC: 38701 AN: 138808 Hom.: 6685 AF XY: 0.281 AC XY: 20832 AN XY: 74138

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 SAS exome AF: 0.347

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.: 25 AF XY: 0.253 AC XY: 164306 AN XY: 649406

Gnomad4 AFR exome AF: 0.0484

Gnomad4 AMR exome AF: 0.334

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.675

Gnomad4 SAS exome AF: 0.345

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.230 AC: 34955 AN: 151700 Hom.: 5393 Cov.: 32 AF XY: 0.243 AC XY: 18027 AN XY: 74088

Gnomad4 AFR AF: 0.0615

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.228

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: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	-0.65
Cadd	Benign	14
Dann	Benign	0.91

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: rs56135050; hg19: chr2-71004494;