rs202673

Variant names:

• chr11-49165627-A-G
• rs202673
• NM_004476.3:c.1373-855T>C

Variant summary

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

The NM_004476.3(FOLH1):​c.1373-855T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 151,914 control chromosomes in the GnomAD database, including 2,985 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 0.18 (2985 hom., cov: 32)
• Consequence: FOLH1 NM_004476.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOLH1	NM_004476.3	c.1373-855T>C		intron_variant	Intron 12 of 18	ENST00000256999.7	NP_004467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOLH1	ENST00000256999.7	c.1373-855T>C		intron_variant	Intron 12 of 18	1	NM_004476.3	ENSP00000256999.2

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27782 AN: 151798 Hom.: 2985 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.183 AC: 27790 AN: 151914 Hom.: 2985 Cov.: 32 AF XY: 0.186 AC XY: 13777 AN XY: 74238

African (AFR) AF: 0.288 AC: 11916 AN: 41378

American (AMR) AF: 0.133 AC: 2035 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 347 AN: 3462

East Asian (EAS) AF: 0.157 AC: 806 AN: 5150

South Asian (SAS) AF: 0.122 AC: 587 AN: 4820

European-Finnish (FIN) AF: 0.225 AC: 2373 AN: 10542

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9285 AN: 67976

Other (OTH) AF: 0.145 AC: 305 AN: 2110

Alfa AF: 0.162 Hom.: 305

Bravo AF: 0.181

Asia WGS AF: 0.127 AC: 441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.31
PhyloP100		0.052
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: rs202673; hg19: chr11-49187179; COSMIC: COSV57046754;