11-72136034-C-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000804.4(FOLR3):c.82C>A(p.Arg28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 1,613,770 control chromosomes in the GnomAD database, including 2,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.080 (722 hom., cov: 32)
  • Exomes 𝑓: 0.049 (2150 hom.)
• Consequence: FOLR3 NM_000804.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.09

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 11-72136034-C-A is Benign according to our data. Variant chr11-72136034-C-A is described in ClinVar as [Benign]. Clinvar id is 3035466.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOLR3	NM_000804.4	c.82C>A	p.Arg28=	synonymous_variant	2/5	ENST00000611028.3
FOLR3	NR_178088.1	n.132C>A		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOLR3	ENST00000611028.3	c.82C>A	p.Arg28=	synonymous_variant	2/5	1	NM_000804.4	P1
FOLR3	ENST00000612844.4	c.82C>A	p.Arg28=	synonymous_variant, NMD_transcript_variant	2/5	1
FOLR3	ENST00000622388.4	c.82C>A	p.Arg28=	synonymous_variant	3/6	5
FOLR3	ENST00000546166.1	c.76C>A	p.Arg26=	synonymous_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12203 AN: 151990 Hom.: 716 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0474

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.0662

GnomAD3 exomes AF: 0.0506 AC: 12671 AN: 250280 Hom.: 479 AF XY: 0.0474 AC XY: 6422 AN XY: 135450

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.0318

Gnomad ASJ exome AF: 0.0420

Gnomad EAS exome AF: 0.0171

Gnomad SAS exome AF: 0.0177

Gnomad FIN exome AF: 0.0952

Gnomad NFE exome AF: 0.0473

Gnomad OTH exome AF: 0.0554

GnomAD4 exome AF: 0.0486 AC: 71037 AN: 1461662 Hom.: 2150 Cov.: 31 AF XY: 0.0474 AC XY: 34446 AN XY: 727120

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.0331

Gnomad4 ASJ exome AF: 0.0427

Gnomad4 EAS exome AF: 0.0112

Gnomad4 SAS exome AF: 0.0174

Gnomad4 FIN exome AF: 0.0950

Gnomad4 NFE exome AF: 0.0474

Gnomad4 OTH exome AF: 0.0530

GnomAD4 genome AF: 0.0804 AC: 12234 AN: 152108 Hom.: 722 Cov.: 32 AF XY: 0.0815 AC XY: 6061 AN XY: 74356

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0405

Gnomad4 ASJ AF: 0.0474

Gnomad4 EAS AF: 0.0158

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0499

Gnomad4 OTH AF: 0.0665

Alfa AF: 0.0535 Hom.: 103

Bravo AF: 0.0785

Asia WGS AF: 0.0360 AC: 123 AN: 3478

EpiCase AF: 0.0438

EpiControl AF: 0.0392

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

FOLR3-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 12, 2019

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
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.34
Dann	Benign	0.80

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: rs1802609; hg19: chr11-71847080;