chr2-70785472-G-A

Position:

• chr2-70785472-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001004311.3(FIGLA):​c.552C>T​(p.His184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,613,550 control chromosomes in the GnomAD database, including 297,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (38151 hom., cov: 32)
  • Exomes 𝑓: 0.59 (259196 hom.)
• Consequence: FIGLA NM_001004311.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.23

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-70785472-G-A is Benign according to our data. Variant chr2-70785472-G-A is described in ClinVar as [Benign]. Clinvar id is 336907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-70785472-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FIGLA	NM_001004311.3	c.552C>T	p.His184=	synonymous_variant	3/5	ENST00000332372.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FIGLA	ENST00000332372.6	c.552C>T	p.His184=	synonymous_variant	3/5	1	NM_001004311.3	P1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105037 AN: 151980 Hom.: 38096 Cov.: 32

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.688

GnomAD3 exomes AF: 0.648 AC: 161622 AN: 249238 Hom.: 54368 AF XY: 0.639 AC XY: 86380 AN XY: 135212

Gnomad AFR exome AF: 0.916

Gnomad AMR exome AF: 0.696

Gnomad ASJ exome AF: 0.553

Gnomad EAS exome AF: 0.910

Gnomad SAS exome AF: 0.676

Gnomad FIN exome AF: 0.665

Gnomad NFE exome AF: 0.555

Gnomad OTH exome AF: 0.617

GnomAD4 exome AF: 0.588 AC: 859620 AN: 1461452 Hom.: 259196 Cov.: 53 AF XY: 0.589 AC XY: 427987 AN XY: 727014

Gnomad4 AFR exome AF: 0.920

Gnomad4 AMR exome AF: 0.692

Gnomad4 ASJ exome AF: 0.548

Gnomad4 EAS exome AF: 0.917

Gnomad4 SAS exome AF: 0.668

Gnomad4 FIN exome AF: 0.661

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.615

GnomAD4 genome AF: 0.691 AC: 105155 AN: 152098 Hom.: 38151 Cov.: 32 AF XY: 0.698 AC XY: 51934 AN XY: 74360

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.690

Alfa AF: 0.583 Hom.: 26499

Bravo AF: 0.704

Asia WGS AF: 0.796 AC: 2768 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Premature ovarian failure 6 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7566541; hg19: chr2-71012604; COSMIC: COSV60089116;