rs6485965

Positions:

• chr11-49145178-A-G
• chr11-49145178-A-T

Variant summary

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

The NM_004476.3(FOLH1):​c.*1578T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 152,050 control chromosomes in the GnomAD database, including 21,895 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 0.52 (21895 hom., cov: 32)
• Consequence: FOLH1 NM_004476.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLH1	NM_004476.3	c.*1578T>C		3_prime_UTR_variant	19/19	ENST00000256999.7	NP_004467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOLH1	ENST00000256999.7	c.*1578T>C		3_prime_UTR_variant	19/19	1	NM_004476.3	ENSP00000256999	P1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78979 AN: 151932 Hom.: 21884 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.520 AC: 79026 AN: 152050 Hom.: 21895 Cov.: 32 AF XY: 0.521 AC XY: 38743 AN XY: 74326

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.576

Alfa AF: 0.571 Hom.: 8589

Bravo AF: 0.517

Asia WGS AF: 0.520 AC: 1810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6485965; hg19: chr11-49166730;