Variant 11-72139409-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

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

Clinical Significance

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

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]

FOLR3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.33 with no splicing effect.

BS1

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

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLR3	NM_000804.4 linkuse as main transcript	c.420G>A	p.Glu140=	synonymous_variant	4/5	ENST00000611028.3	NP_000795.2
FOLR3	NR_178088.1 linkuse as main transcript	n.598G>A		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOLR3	ENST00000611028.3 linkuse as main transcript	c.420G>A	p.Glu140=	synonymous_variant	4/5	1	NM_000804.4	ENSP00000481114	P1	P41439-1
FOLR3	ENST00000612844.4 linkuse as main transcript	c.*29G>A		3_prime_UTR_variant, NMD_transcript_variant	4/5	1		ENSP00000481027		P41439-4
FOLR3	ENST00000622388.4 linkuse as main transcript	c.420G>A	p.Glu140=	synonymous_variant	5/6	5		ENSP00000481833
FOLR3	ENST00000545379.1 linkuse as main transcript	n.160G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00558

AC:

850

AN:

152228

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00564

AC:

859

AN:

152346

Hom.:

Cov.:

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.:

Bravo

AF:

0.00667

Asia WGS

AF:

0.0140

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 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.

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