11-49171138-T-C

Position:

• chr11-49171138-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004476.3(FOLH1):​c.1308+57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,478,334 control chromosomes in the GnomAD database, including 17,548 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 (2919 hom., cov: 31)
  • Exomes 𝑓: 0.14 (14629 hom.)
• Consequence: FOLH1 NM_004476.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLH1	NM_004476.3	c.1308+57A>G		intron_variant		ENST00000256999.7	NP_004467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOLH1	ENST00000256999.7	c.1308+57A>G		intron_variant		1	NM_004476.3	ENSP00000256999.2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27570 AN: 151938 Hom.: 2918 Cov.: 31

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.144 AC: 191381 AN: 1326278 Hom.: 14629 AF XY: 0.143 AC XY: 93822 AN XY: 655474

Gnomad4 AFR exome AF: 0.285

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.0939

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.181 AC: 27579 AN: 152056 Hom.: 2919 Cov.: 31 AF XY: 0.184 AC XY: 13676 AN XY: 74312

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.143

Alfa AF: 0.156 Hom.: 268

Bravo AF: 0.179

Asia WGS AF: 0.128 AC: 442 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.83
DANN	Benign	0.83

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: rs202719; hg19: chr11-49192690; COSMIC: COSV57051356;