11-49170799-G-C

Variant names:

• chr11-49170799-G-C
• rs202720
• NM_004476.3:c.1308+396C>G

Variant summary

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

The NM_004476.3(FOLH1):​c.1308+396C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,946 control chromosomes in the GnomAD database, including 10,083 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 0.33 (10083 hom., cov: 32)
• Consequence: FOLH1 NM_004476.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLH1	NM_004476.3	MANE Select	c.1308+396C>G		intron	N/A	NP_004467.1	Q04609-1
	FOLH1	NM_001193471.3		c.1263+396C>G		intron	N/A	NP_001180400.1	Q04609-7
	FOLH1	NM_001014986.3		c.1308+396C>G		intron	N/A	NP_001014986.1	Q04609-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLH1	ENST00000256999.7	TSL:1 MANE Select	c.1308+396C>G		intron	N/A	ENSP00000256999.2	Q04609-1
	FOLH1	ENST00000340334.11	TSL:1	c.1263+396C>G		intron	N/A	ENSP00000344131.7	Q04609-7
	FOLH1	ENST00000356696.7	TSL:1	c.1308+396C>G		intron	N/A	ENSP00000349129.3	Q04609-8

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50631 AN: 151828 Hom.: 10071 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.334 AC: 50679 AN: 151946 Hom.: 10083 Cov.: 32 AF XY: 0.336 AC XY: 24965 AN XY: 74256

African (AFR) AF: 0.562 AC: 23273 AN: 41432

American (AMR) AF: 0.258 AC: 3933 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 630 AN: 3466

East Asian (EAS) AF: 0.321 AC: 1658 AN: 5160

South Asian (SAS) AF: 0.360 AC: 1736 AN: 4828

European-Finnish (FIN) AF: 0.298 AC: 3131 AN: 10524

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.229 AC: 15537 AN: 67956

Other (OTH) AF: 0.275 AC: 580 AN: 2110

Alfa AF: 0.120 Hom.: 189

Bravo AF: 0.336

Asia WGS AF: 0.387 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.26
PhyloP100		-0.019
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: rs202720; hg19: chr11-49192351;