2-70777956-A-G

Variant names:

• chr2-70777956-A-G
• rs79211746
• NM_001004311.3:c.610-285T>C

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.610-285T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 152,202 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.040 (195 hom., cov: 32)
• Consequence: FIGLA NM_001004311.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.106
• Publications: 0 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=-0.73).
• BP6: Variant 2-70777956-A-G is Benign according to our data. Variant chr2-70777956-A-G is described in ClinVar as [Benign]. Clinvar id is 1249607.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGLA	NM_001004311.3	c.610-285T>C		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.610-285T>C		intron_variant	Intron 3 of 4	1	NM_001004311.3	ENSP00000333097.6

Frequencies

GnomAD3 genomes AF: 0.0401 AC: 6096 AN: 152084 Hom.: 195 Cov.: 32

Gnomad AFR AF: 0.0867

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0227

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.0311

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

GnomAD4 genome AF: 0.0401 AC: 6104 AN: 152202 Hom.: 195 Cov.: 32 AF XY: 0.0404 AC XY: 3002 AN XY: 74396

African (AFR) AF: 0.0867 AC: 3599 AN: 41512

American (AMR) AF: 0.0226 AC: 345 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3466

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0158 AC: 76 AN: 4824

European-Finnish (FIN) AF: 0.0368 AC: 390 AN: 10594

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0225 AC: 1528 AN: 68010

Other (OTH) AF: 0.0308 AC: 65 AN: 2112

Alfa AF: 0.0305 Hom.: 19

Bravo AF: 0.0406

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 14, 2019

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	-0.73
CADD	Benign	6.7
DANN	Benign	0.79
PhyloP100		0.11
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: rs79211746; hg19: chr2-71005088;