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GeneBe

11-72139409-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000804.4(FOLR3):c.420G>A(p.Glu140=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,612,020 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 38 hom., cov: 32)
Exomes 𝑓: 0.0022 ( 70 hom. )

Consequence

FOLR3
NM_000804.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.33
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-72139409-G-A is Benign according to our data. Variant chr11-72139409-G-A is described in ClinVar as [Benign]. Clinvar id is 773826.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.33 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00564 (859/152346) while in subpopulation AMR AF= 0.04 (613/15310). AF 95% confidence interval is 0.0374. There are 38 homozygotes in gnomad4. There are 531 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 38 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FOLR3NM_000804.4 linkuse as main transcriptc.420G>A p.Glu140= synonymous_variant 4/5 ENST00000611028.3
FOLR3NR_178088.1 linkuse as main transcriptn.598G>A non_coding_transcript_exon_variant 4/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOLR3ENST00000611028.3 linkuse as main transcriptc.420G>A p.Glu140= synonymous_variant 4/51 NM_000804.4 P1P41439-1
FOLR3ENST00000612844.4 linkuse as main transcriptc.*29G>A 3_prime_UTR_variant, NMD_transcript_variant 4/51 P41439-4
FOLR3ENST00000622388.4 linkuse as main transcriptc.420G>A p.Glu140= synonymous_variant 5/65
FOLR3ENST00000545379.1 linkuse as main transcriptn.160G>A non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00558
AC:
850
AN:
152228
Hom.:
38
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000434
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0395
Gnomad ASJ
AF:
0.00346
Gnomad EAS
AF:
0.0281
Gnomad SAS
AF:
0.00207
Gnomad FIN
AF:
0.00273
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.00526
GnomAD3 exomes
AF:
0.00623
AC:
1529
AN:
245516
Hom.:
44
AF XY:
0.00517
AC XY:
687
AN XY:
133000
show subpopulations
Gnomad AFR exome
AF:
0.000327
Gnomad AMR exome
AF:
0.0255
Gnomad ASJ exome
AF:
0.00231
Gnomad EAS exome
AF:
0.0263
Gnomad SAS exome
AF:
0.00152
Gnomad FIN exome
AF:
0.00205
Gnomad NFE exome
AF:
0.000452
Gnomad OTH exome
AF:
0.00400
GnomAD4 exome
AF:
0.00221
AC:
3220
AN:
1459674
Hom.:
70
Cov.:
33
AF XY:
0.00208
AC XY:
1508
AN XY:
726022
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.0269
Gnomad4 ASJ exome
AF:
0.00184
Gnomad4 EAS exome
AF:
0.0328
Gnomad4 SAS exome
AF:
0.00163
Gnomad4 FIN exome
AF:
0.00193
Gnomad4 NFE exome
AF:
0.000264
Gnomad4 OTH exome
AF:
0.00224
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00564
AC:
859
AN:
152346
Hom.:
38
Cov.:
32
AF XY:
0.00713
AC XY:
531
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.000433
Gnomad4 AMR
AF:
0.0400
Gnomad4 ASJ
AF:
0.00346
Gnomad4 EAS
AF:
0.0282
Gnomad4 SAS
AF:
0.00207
Gnomad4 FIN
AF:
0.00273
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.000819
Hom.:
0
Bravo
AF:
0.00667
Asia WGS
AF:
0.0140
AC:
48
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
Cadd
Benign
8.2
Dann
Benign
0.54

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.

Other links and lift over

dbSNP: rs79284835; hg19: chr11-71850453; API