NM_001004311.3:c.609+327C>T

Variant names:

• chr2-70785088-G-A
• rs6546631
• NM_001004311.3:c.609+327C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001004311.3(FIGLA):​c.609+327C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,252 control chromosomes in the GnomAD database, including 22,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.53 (22238 hom., cov: 30)
• Consequence: FIGLA NM_001004311.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.67
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-70785088-G-A is Benign according to our data. Variant chr2-70785088-G-A is described in ClinVar as [Benign]. Clinvar id is 1183788.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGLA	NM_001004311.3	c.609+327C>T		intron_variant	Intron 3 of 4	ENST00000332372.6	NP_001004311.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIGLA	ENST00000332372.6	c.609+327C>T		intron_variant	Intron 3 of 4	1	NM_001004311.3	ENSP00000333097.6

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80219 AN: 151134 Hom.: 22223 Cov.: 30

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.531 AC: 80286 AN: 151252 Hom.: 22238 Cov.: 30 AF XY: 0.541 AC XY: 39948 AN XY: 73880

African (AFR) AF: 0.666 AC: 27458 AN: 41226

American (AMR) AF: 0.533 AC: 8113 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1631 AN: 3460

East Asian (EAS) AF: 0.738 AC: 3797 AN: 5148

South Asian (SAS) AF: 0.556 AC: 2646 AN: 4762

European-Finnish (FIN) AF: 0.595 AC: 6193 AN: 10404

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28711 AN: 67726

Other (OTH) AF: 0.533 AC: 1123 AN: 2106

Alfa AF: 0.483 Hom.: 2303

Bravo AF: 0.533

Asia WGS AF: 0.567 AC: 1611 AN: 2838

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: 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	-0.81
CADD	Benign	0.88
DANN	Benign	0.64
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6546631; hg19: chr2-71012220;