dbSNP rs2298444: FOLR2:c.475+59T>C (chr11-72221370-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000803.5(FOLR2):c.475+59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,600,206 control chromosomes in the GnomAD database, including 40,465 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6466 hom., cov: 31)

Exomes 𝑓: 0.21 ( 33999 hom. )

Consequence

FOLR2
NM_000803.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.882

Publications

16 publications found

Variant links:

Genes affected

FOLR2 (HGNC:3793): (folate receptor beta) The protein encoded by this gene is a member of the folate receptor (FOLR) family, and these genes exist in a cluster on chromosome 11. Members of this gene family have a high affinity for folic acid and for several reduced folic acid derivatives, and they mediate delivery of 5-methyltetrahydrofolate to the interior of cells. This protein has a 68% and 79% sequence homology with the FOLR1 and FOLR3 proteins, respectively. Although this protein was originally thought to be specific to placenta, it can also exist in other tissues, and it may play a role in the transport of methotrexate in synovial macrophages in rheumatoid arthritis patients. Multiple transcript variants that encode the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

FOLR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOLR2	NM_000803.5 link	c.475+59T>C		intron_variant	Intron 4 of 4	ENST00000298223.11	NP_000794.3	P14207

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOLR2	ENST00000298223.11 link	c.475+59T>C		intron_variant	Intron 4 of 4	1	NM_000803.5	ENSP00000298223.6		P14207

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40624

AN:

151856

Hom.:

6457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.433

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.374

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.218

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.179

Gnomad OTH

AF:

0.222

GnomAD4 exome

AF:

0.206

AC:

298960

AN:

1448232

Hom.:

33999

Cov.:

AF XY:

0.210

AC XY:

151047

AN XY:

718588

show subpopulations

African (AFR)

AF:

0.450

AC:

14865

AN:

33010

American (AMR)

AF:

0.221

AC:

9654

AN:

43684

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

4295

AN:

25420

East Asian (EAS)

AF:

0.331

AC:

13045

AN:

39456

South Asian (SAS)

AF:

0.362

AC:

30809

AN:

85156

European-Finnish (FIN)

AF:

0.211

AC:

11126

AN:

52734

Middle Eastern (MID)

AF:

0.280

AC:

1596

AN:

5708

European-Non Finnish (NFE)

AF:

0.182

AC:

200363

AN:

1103454

Other (OTH)

AF:

0.222

AC:

13207

AN:

59610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

14137

28273

42410

56546

70683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7478

14956

22434

29912

37390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.268

AC:

40668

AN:

151974

Hom.:

6466

Cov.:

AF XY:

0.271

AC XY:

20174

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.433

AC:

17922

AN:

41410

American (AMR)

AF:

0.221

AC:

3381

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

612

AN:

3470

East Asian (EAS)

AF:

0.374

AC:

1923

AN:

5144

South Asian (SAS)

AF:

0.373

AC:

1796

AN:

4820

European-Finnish (FIN)

AF:

0.218

AC:

2304

AN:

10586

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.179

AC:

12132

AN:

67956

Other (OTH)

AF:

0.230

AC:

484

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1416

2832

4249

5665

7081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.215

Hom.:

5938

Bravo

AF:

0.273

Asia WGS

AF:

0.400

AC:

1390

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.59

(source)

DANN

Benign

0.43

PhyloP100

-0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over