11-49171115-C-T

Variant names:

• chr11-49171115-C-T
• rs10839236
• NM_004476.3:c.1308+80G>A

Variant summary

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

The NM_004476.3(FOLH1):​c.1308+80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,419,152 control chromosomes in the GnomAD database, including 237,145 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 0.50 (20987 hom., cov: 32)
  • Exomes 𝑓: 0.58 (216158 hom.)
• Consequence: FOLH1 NM_004476.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOLH1	NM_004476.3	c.1308+80G>A		intron_variant	Intron 11 of 18	ENST00000256999.7	NP_004467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOLH1	ENST00000256999.7	c.1308+80G>A		intron_variant	Intron 11 of 18	1	NM_004476.3	ENSP00000256999.2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75457 AN: 151838 Hom.: 20976 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.600

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.555

GnomAD4 exome AF: 0.580 AC: 734946 AN: 1267194 Hom.: 216158 AF XY: 0.581 AC XY: 362790 AN XY: 624384

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.643

Gnomad4 ASJ exome AF: 0.715

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.550

Gnomad4 FIN exome AF: 0.565

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.570

GnomAD4 genome AF: 0.497 AC: 75483 AN: 151958 Hom.: 20987 Cov.: 32 AF XY: 0.499 AC XY: 37042 AN XY: 74256

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.560

Alfa AF: 0.545 Hom.: 3000

Bravo AF: 0.492

Asia WGS AF: 0.509 AC: 1764 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.16

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: rs10839236; hg19: chr11-49192667;