Variant 11-49200333-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004476.3(FOLH1):c.333A>T(p.Ala111=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,608,196 control chromosomes in the GnomAD database, including 79,396 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 0.36 ( 11305 hom., cov: 32)

Exomes 𝑓: 0.30 ( 68091 hom. )

Consequence

FOLH1
NM_004476.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.414

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP7

Synonymous conserved (PhyloP=0.414 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLH1	NM_004476.3 linkuse as main transcript	c.333A>T	p.Ala111=	synonymous_variant	3/19	ENST00000256999.7	NP_004467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOLH1	ENST00000256999.7 linkuse as main transcript	c.333A>T	p.Ala111=	synonymous_variant	3/19	1	NM_004476.3	ENSP00000256999	P1	Q04609-1

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55309

AN:

151860

Hom.:

11292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.561

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.330

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.319

GnomAD3 exomes

AF:

0.311

AC:

76763

AN:

246472

Hom.:

12862

AF XY:

0.309

AC XY:

41204

AN XY:

133226

show subpopulations

Gnomad AFR exome

AF:

0.563

Gnomad AMR exome

AF:

0.277

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.298

Gnomad SAS exome

AF:

0.394

Gnomad FIN exome

AF:

0.331

Gnomad NFE exome

AF:

0.275

Gnomad OTH exome

AF:

0.266

GnomAD4 exome

AF:

0.300

AC:

436987

AN:

1456218

Hom.:

68091

Cov.:

AF XY:

0.301

AC XY:

217988

AN XY:

724234

show subpopulations

Gnomad4 AFR exome

AF:

0.572

Gnomad4 AMR exome

AF:

0.282

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.329

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.286

Gnomad4 OTH exome

AF:

0.309

GnomAD4 genome

AF:

0.364

AC:

55360

AN:

151978

Hom.:

11305

Cov.:

AF XY:

0.366

AC XY:

27170

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.561

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.201

Gnomad4 EAS

AF:

0.322

Gnomad4 SAS

AF:

0.398

Gnomad4 FIN

AF:

0.330

Gnomad4 NFE

AF:

0.280

Gnomad4 OTH

AF:

0.316

Alfa

AF:

0.290

Hom.:

2271

Bravo

AF:

0.365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.3

DANN

Benign

0.45

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over