11-49195147-C-T

Position:

• chr11-49195147-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FOLH1	NM_004476.3	c.412-2253G>A		intron_variant		ENST00000256999.7	NP_004467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOLH1	ENST00000256999.7	c.412-2253G>A		intron_variant		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

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.317

Alfa AF: 0.304 Hom.: 3877

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

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

Other links and lift over

dbSNP: rs202700; hg19: chr11-49216699;