dbSNP rs188821779: FOLR3:p.Glu108Asp (chr11-72139116-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000804.4(FOLR3):c.324G>C(p.Glu108Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00121 in 1,613,886 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 12 hom. )

Consequence

FOLR3
NM_000804.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.83

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011602581).

BP6

Variant 11-72139116-G-C is Benign according to our data. Variant chr11-72139116-G-C is described in ClinVar as [Benign]. Clinvar id is 711557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00648 (987/152330) while in subpopulation AFR AF= 0.0223 (925/41566). AF 95% confidence interval is 0.0211. There are 15 homozygotes in gnomad4. There are 461 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOLR3	NM_000804.4 link	c.324G>C	p.Glu108Asp	missense_variant	Exon 3 of 5	ENST00000611028.3	NP_000795.2	P41439-1
FOLR3	NR_178088.1 link	n.502G>C		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.324G>C	p.Glu108Asp	missense_variant	Exon 3 of 5	1	NM_000804.4	ENSP00000481114.1		P41439-1

Frequencies

GnomAD3 genomes

AF:

0.00646

AC:

983

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00159

AC:

397

AN:

250462

Hom.:

AF XY:

0.00122

AC XY:

165

AN XY:

135496

show subpopulations

Gnomad AFR exome

AF:

0.0225

Gnomad AMR exome

AF:

0.000897

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000663

AC:

969

AN:

1461556

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

411

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.0237

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.00648

AC:

987

AN:

152330

Hom.:

Cov.:

AF XY:

0.00619

AC XY:

461

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0223

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00183

Hom.:

Bravo

AF:

0.00683

ExAC

AF:

0.00191

AC:

232

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Pathogenic

0.17

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

D;.

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

D;D

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.41

PrimateAI

Benign

0.48

Sift4G

Uncertain

0.0060

D;D

Vest4

0.70

MVP

0.33

ClinPred

0.027

GERP RS

2.3

gMVP

0.81

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

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