11-72136105-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000804.4(FOLR3):c.153C>T(p.Asp51=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 1,614,040 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (105 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (87 hom.)
• Consequence: FOLR3 NM_000804.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00400

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 11-72136105-C-T is Benign according to our data. Variant chr11-72136105-C-T is described in ClinVar as [Benign]. Clinvar id is 785366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.004 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOLR3	NM_000804.4	c.153C>T	p.Asp51=	synonymous_variant	2/5	ENST00000611028.3
FOLR3	NR_178088.1	n.203C>T		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOLR3	ENST00000611028.3	c.153C>T	p.Asp51=	synonymous_variant	2/5	1	NM_000804.4	P1
FOLR3	ENST00000612844.4	c.153C>T	p.Asp51=	synonymous_variant, NMD_transcript_variant	2/5	1
FOLR3	ENST00000622388.4	c.153C>T	p.Asp51=	synonymous_variant	3/6	5
FOLR3	ENST00000546166.1	c.147C>T	p.Asp49=	synonymous_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 3004 AN: 152144 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00517 AC: 1293 AN: 250254 Hom.: 38 AF XY: 0.00392 AC XY: 531 AN XY: 135340

Gnomad AFR exome AF: 0.0703

Gnomad AMR exome AF: 0.00347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00279

GnomAD4 exome AF: 0.00194 AC: 2836 AN: 1461778 Hom.: 87 Cov.: 31 AF XY: 0.00166 AC XY: 1209 AN XY: 727176

Gnomad4 AFR exome AF: 0.0683

Gnomad4 AMR exome AF: 0.00398

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000863

Gnomad4 OTH exome AF: 0.00401

GnomAD4 genome AF: 0.0198 AC: 3012 AN: 152262 Hom.: 105 Cov.: 32 AF XY: 0.0189 AC XY: 1409 AN XY: 74454

Gnomad4 AFR AF: 0.0691

Gnomad4 AMR AF: 0.00627

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00965 Hom.: 14

Bravo AF: 0.0224

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

FOLR3-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 02, 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	-0.76
Cadd	Benign	2.9
Dann	Benign	0.68

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: rs151190708; hg19: chr11-71847151; COSMIC: COSV61530718; COSMIC: COSV61530718;