11-49152589-G-T

Position:

• chr11-49152589-G-T

Variant summary

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

The NM_004476.3(FOLH1):​c.1970+1257C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,202 control chromosomes in the GnomAD database, including 60,468 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 0.89 (60468 hom., cov: 33)
• Consequence: FOLH1 NM_004476.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLH1	NM_004476.3	c.1970+1257C>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.1970+1257C>A		intron_variant		1	NM_004476.3	ENSP00000256999	P1

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135538 AN: 152084 Hom.: 60427 Cov.: 33

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.899

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

GnomAD4 genome AF: 0.891 AC: 135634 AN: 152202 Hom.: 60468 Cov.: 33 AF XY: 0.893 AC XY: 66499 AN XY: 74426

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.918

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.900

Gnomad4 SAS AF: 0.952

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.901

Alfa AF: 0.884 Hom.: 12036

Bravo AF: 0.890

Asia WGS AF: 0.920 AC: 3188 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.30

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: rs383028; hg19: chr11-49174141;