rs145924266

Positions:

• chr3-138946973-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_023067.4(FOXL2):​c.-251G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 561,014 control chromosomes in the GnomAD database, including 914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (415 hom., cov: 32)
  • Exomes 𝑓: 0.013 (499 hom.)
• Consequence: FOXL2 NM_023067.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.785

Genes affected

FOXL2 (HGNC:1092): (forkhead box L2) This gene encodes a forkhead transcription factor. The protein contains a fork-head DNA-binding domain and may play a role in ovarian development and function. Expansion of a polyalanine repeat region and other mutations in this gene are a cause of blepharophimosis syndrome and premature ovarian failure 3. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 3-138946973-C-T is Benign according to our data. Variant chr3-138946973-C-T is described in ClinVar as [Benign]. Clinvar id is 261660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXL2	NM_023067.4	c.-251G>A		5_prime_UTR_variant	1/1	ENST00000648323.1	NP_075555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXL2	ENST00000648323.1	c.-251G>A		5_prime_UTR_variant	1/1		NM_023067.4	ENSP00000497217.1

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4165 AN: 152104 Hom.: 411 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0234

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0378

GnomAD4 exome AF: 0.0133 AC: 5453 AN: 408792 Hom.: 499 Cov.: 5 AF XY: 0.0130 AC XY: 2767 AN XY: 212262

Gnomad4 AFR exome AF: 0.0169

Gnomad4 AMR exome AF: 0.257

Gnomad4 ASJ exome AF: 0.0000817

Gnomad4 EAS exome AF: 0.0317

Gnomad4 SAS exome AF: 0.0179

Gnomad4 FIN exome AF: 0.000159

Gnomad4 NFE exome AF: 0.000956

Gnomad4 OTH exome AF: 0.0177

GnomAD4 genome AF: 0.0274 AC: 4177 AN: 152222 Hom.: 415 Cov.: 32 AF XY: 0.0311 AC XY: 2313 AN XY: 74424

Gnomad4 AFR AF: 0.0181

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0236

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0193 Hom.: 28

Bravo AF: 0.0446

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

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	-0.57
CADD	Benign	16
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs145924266; hg19: chr3-138665815;