NM_004476.3:c.412-2253G>A

Variant names:

• chr11-49195147-C-T
• rs202700
• NM_004476.3:c.412-2253G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004476.3(FOLH1):​c.412-2253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,776 control chromosomes in the GnomAD database, including 11,261 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 (11261 hom., cov: 32)
• Consequence: FOLH1 NM_004476.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 6 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• 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 rank	MANE	Protein	UniProt
FOLH1	NM_004476.3	c.412-2253G>A		intron_variant	Intron 3 of 18	ENST00000256999.7	NP_004467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOLH1	ENST00000256999.7	c.412-2253G>A		intron_variant	Intron 3 of 18	1	NM_004476.3	ENSP00000256999.2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55164 AN: 151660 Hom.: 11248 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.320

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.364 AC: 55214 AN: 151776 Hom.: 11261 Cov.: 32 AF XY: 0.366 AC XY: 27110 AN XY: 74164

African (AFR) AF: 0.561 AC: 23211 AN: 41396

American (AMR) AF: 0.291 AC: 4431 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 694 AN: 3464

East Asian (EAS) AF: 0.320 AC: 1647 AN: 5148

South Asian (SAS) AF: 0.395 AC: 1898 AN: 4810

European-Finnish (FIN) AF: 0.330 AC: 3472 AN: 10508

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 18981 AN: 67898

Other (OTH) AF: 0.317 AC: 668 AN: 2108

Alfa AF: 0.306 Hom.: 5395

Bravo AF: 0.365

Asia WGS AF: 0.400 AC: 1383 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.42
DANN	Benign	0.31
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs202700; hg19: chr11-49216699;