Genetic Variant NM_000804.4:c.292C>T (chr11-72139084-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000804.4(FOLR3):c.292C>T(p.Arg98Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 1,594,208 control chromosomes in the GnomAD database, including 2,020 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.040 ( 125 hom., cov: 33)

Exomes 𝑓: 0.048 ( 1895 hom. )

Consequence

FOLR3
NM_000804.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.26

Variant links:

Genes affected

FOLR3 (HGNC:3795): (folate receptor gamma) This gene encodes a member of the folate receptor (FOLR) family of proteins, which have a high affinity for folic acid and for several reduced folic acid derivatives, and mediate delivery of 5-methyltetrahydrofolate to the interior of cells. Expression of this gene may be elevated in ovarian and primary peritoneal carcinoma. This gene is present in a gene cluster on chromosome 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

FOLR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039766133).

BP6

Variant 11-72139084-C-T is Benign according to our data. Variant chr11-72139084-C-T is described in ClinVar as [Benign]. Clinvar id is 3035503.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOLR3	NM_000804.4 link	c.292C>T	p.Arg98Cys	missense_variant	Exon 3 of 5	ENST00000611028.3	NP_000795.2	P41439-1
FOLR3	NR_178088.1 link	n.470C>T		non_coding_transcript_exon_variant	Exon 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOLR3	ENST00000611028.3 link	c.292C>T	p.Arg98Cys	missense_variant	Exon 3 of 5	1	NM_000804.4	ENSP00000481114.1		P41439-1

Frequencies

GnomAD3 genomes

AF:

0.0404

AC:

5344

AN:

132416

Hom.:

125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0126

Gnomad AMI

AF:

0.00383

Gnomad AMR

AF:

0.0518

Gnomad ASJ

AF:

0.0414

Gnomad EAS

AF:

0.000467

Gnomad SAS

AF:

0.0347

Gnomad FIN

AF:

0.0412

Gnomad MID

AF:

0.0374

Gnomad NFE

AF:

0.0574

Gnomad OTH

AF:

0.0530

GnomAD3 exomes

AF:

0.0350

AC:

8787

AN:

251052

Hom.:

209

AF XY:

0.0360

AC XY:

4887

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.00925

Gnomad AMR exome

AF:

0.0245

Gnomad ASJ exome

AF:

0.0405

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0262

Gnomad FIN exome

AF:

0.0338

Gnomad NFE exome

AF:

0.0494

Gnomad OTH exome

AF:

0.0389

GnomAD4 exome

AF:

0.0483

AC:

70635

AN:

1461662

Hom.:

1895

Cov.:

AF XY:

0.0478

AC XY:

34765

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.00884

Gnomad4 AMR exome

AF:

0.0269

Gnomad4 ASJ exome

AF:

0.0390

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0270

Gnomad4 FIN exome

AF:

0.0329

Gnomad4 NFE exome

AF:

0.0549

Gnomad4 OTH exome

AF:

0.0458

GnomAD4 genome

AF:

0.0403

AC:

5343

AN:

132546

Hom.:

125

Cov.:

AF XY:

0.0393

AC XY:

2507

AN XY:

63734

show subpopulations

Gnomad4 AFR

AF:

0.0125

Gnomad4 AMR

AF:

0.0517

Gnomad4 ASJ

AF:

0.0414

Gnomad4 EAS

AF:

0.000468

Gnomad4 SAS

AF:

0.0346

Gnomad4 FIN

AF:

0.0412

Gnomad4 NFE

AF:

0.0574

Gnomad4 OTH

AF:

0.0513

Alfa

AF:

0.0437

Hom.:

101

Bravo

AF:

0.0340

TwinsUK

AF:

0.0491

AC:

182

ALSPAC

AF:

0.0568

AC:

219

ESP6500AA

AF:

0.00795

AC:

ESP6500EA

AF:

0.0531

AC:

456

ExAC

AF:

0.0350

AC:

4248

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.0551

EpiControl

AF:

0.0511

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FOLR3-related disorder

Benign:1

May 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.41

T;.;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.74

T;T;T

MetaRNN

Benign

0.0040

T;T;T

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.28

REVEL

Benign

0.18

Sift4G

Uncertain

0.0020

D;D;D

Vest4

0.23, 0.14

ClinPred

0.0085

GERP RS

-1.2

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over