rs7566541

Variant names:

• chr2-70785472-G-A
• rs7566541
• NM_001004311.3:c.552C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-70785472-G-A
• chr2-70785472-G-C
• chr2-70785472-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000332372.6(FIGLA):​c.552C>T​(p.His184His) 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 ENST00000332372.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.23
• Publications: 16 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 336907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000332372.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIGLA	NM_001004311.3	MANE Select	c.552C>T	p.His184His	synonymous	Exon 3 of 5	NP_001004311.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIGLA	ENST00000332372.6	TSL:1 MANE Select	c.552C>T	p.His184His	synonymous	Exon 3 of 5	ENSP00000333097.6

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

GnomAD2 exomes AF: 0.648 AC: 161622 AN: 249238 AF XY: 0.639

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 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

African (AFR) AF: 0.920 AC: 30818 AN: 33480

American (AMR) AF: 0.692 AC: 30933 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 14324 AN: 26132

East Asian (EAS) AF: 0.917 AC: 36400 AN: 39700

South Asian (SAS) AF: 0.668 AC: 57572 AN: 86242

European-Finnish (FIN) AF: 0.661 AC: 35310 AN: 53400

Middle Eastern (MID) AF: 0.643 AC: 3709 AN: 5766

European-Non Finnish (NFE) AF: 0.552 AC: 613429 AN: 1111644

Other (OTH) AF: 0.615 AC: 37125 AN: 60364

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

African (AFR) AF: 0.908 AC: 37681 AN: 41518

American (AMR) AF: 0.673 AC: 10281 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1938 AN: 3466

East Asian (EAS) AF: 0.910 AC: 4710 AN: 5178

South Asian (SAS) AF: 0.686 AC: 3304 AN: 4814

European-Finnish (FIN) AF: 0.679 AC: 7174 AN: 10560

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.557 AC: 37870 AN: 67968

Other (OTH) AF: 0.690 AC: 1458 AN: 2114

Alfa AF: 0.600 Hom.: 36875

Bravo AF: 0.704

Asia WGS AF: 0.796 AC: 2768 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Premature ovarian failure 6 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.62
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7566541; hg19: chr2-71012604; COSMIC: COSV60089116;