chr11-49165732-G-A

Position:

• chr11-49165732-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004476.3(FOLH1):​c.1373-960C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0337 in 152,196 control chromosomes in the GnomAD database, including 123 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 0.034 (123 hom., cov: 33)
• Consequence: FOLH1 NM_004476.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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=-0.98).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0337 (5131/152196) while in subpopulation NFE AF= 0.0513 (3489/68002). AF 95% confidence interval is 0.0499. There are 123 homozygotes in gnomad4. There are 2441 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 123 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLH1	NM_004476.3	c.1373-960C>T		intron_variant		ENST00000256999.7	NP_004467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOLH1	ENST00000256999.7	c.1373-960C>T		intron_variant		1	NM_004476.3	ENSP00000256999.2

Frequencies

GnomAD3 genomes AF: 0.0337 AC: 5131 AN: 152078 Hom.: 123 Cov.: 33

Gnomad AFR AF: 0.00864

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0358

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.0343

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0513

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0337 AC: 5131 AN: 152196 Hom.: 123 Cov.: 33 AF XY: 0.0328 AC XY: 2441 AN XY: 74434

Gnomad4 AFR AF: 0.00862

Gnomad4 AMR AF: 0.0358

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0398

Gnomad4 FIN AF: 0.0343

Gnomad4 NFE AF: 0.0513

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.0452 Hom.: 36

Bravo AF: 0.0318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.1
DANN	Benign	0.51

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: rs7113251; hg19: chr11-49187284;