chr11-49146902-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004476.3(FOLH1):c.2107G>A(p.Glu703Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FOLH1
NM_004476.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.01

Publications

3 publications found

Variant links:

Genes affected

FOLH1 (HGNC:3788): (folate hydrolase 1) This gene encodes a type II transmembrane glycoprotein belonging to the M28 peptidase family. The protein acts as a glutamate carboxypeptidase on different alternative substrates, including the nutrient folate and the neuropeptide N-acetyl-l-aspartyl-l-glutamate and is expressed in a number of tissues such as prostate, central and peripheral nervous system and kidney. A mutation in this gene may be associated with impaired intestinal absorption of dietary folates, resulting in low blood folate levels and consequent hyperhomocysteinemia. Expression of this protein in the brain may be involved in a number of pathological conditions associated with glutamate excitotoxicity. In the prostate the protein is up-regulated in cancerous cells and is used as an effective diagnostic and prognostic indicator of prostate cancer. This gene likely arose from a duplication event of a nearby chromosomal region. Alternative splicing gives rise to multiple transcript variants encoding several different isoforms. [provided by RefSeq, Jul 2010]

FOLH1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3486051).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004476.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOLH1	NM_004476.3	MANE Select	c.2107G>A	p.Glu703Lys	missense	Exon 19 of 19	NP_004467.1	Q04609-1
FOLH1	NM_001193471.3		c.2062G>A	p.Glu688Lys	missense	Exon 20 of 20	NP_001180400.1	Q04609-7
FOLH1	NM_001014986.3		c.2014G>A	p.Glu672Lys	missense	Exon 18 of 18	NP_001014986.1	Q04609-8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOLH1	ENST00000256999.7	TSL:1 MANE Select	c.2107G>A	p.Glu703Lys	missense	Exon 19 of 19	ENSP00000256999.2	Q04609-1
FOLH1	ENST00000340334.11	TSL:1	c.2062G>A	p.Glu688Lys	missense	Exon 20 of 20	ENSP00000344131.7	Q04609-7
FOLH1	ENST00000356696.7	TSL:1	c.2014G>A	p.Glu672Lys	missense	Exon 18 of 18	ENSP00000349129.3	Q04609-8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250380

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726760

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33404

American (AMR)

AF:

0.00

AC:

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111416

Other (OTH)

AF:

0.00

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

0.13

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.018

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.2

PhyloP100

4.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.0

REVEL

Benign

0.17

Sift

Benign

0.033

Sift4G

Benign

0.65

Polyphen

0.38

Vest4

0.55

MutPred

0.67

Gain of ubiquitination at E703 (P = 0.017)

MVP

0.63

MPC

2.2

ClinPred

0.84

GERP RS

3.3

Varity_R

0.27

gMVP

0.87

Mutation Taster

=56/44

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over