NM_004476.3:c.1308+80G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004476.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLH1	NM_004476.3	MANE Select	c.1308+80G>A		intron	N/A	NP_004467.1
	FOLH1	NM_001193471.3		c.1263+80G>A		intron	N/A	NP_001180400.1
	FOLH1	NM_001014986.3		c.1308+80G>A		intron	N/A	NP_001014986.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLH1	ENST00000256999.7	TSL:1 MANE Select	c.1308+80G>A		intron	N/A	ENSP00000256999.2
	FOLH1	ENST00000340334.11	TSL:1	c.1263+80G>A		intron	N/A	ENSP00000344131.7
	FOLH1	ENST00000356696.7	TSL:1	c.1308+80G>A		intron	N/A	ENSP00000349129.3

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

African (AFR) AF: 0.206 AC: 5552 AN: 27000

American (AMR) AF: 0.643 AC: 17486 AN: 27198

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 15085 AN: 21092

East Asian (EAS) AF: 0.583 AC: 20045 AN: 34364

South Asian (SAS) AF: 0.550 AC: 31837 AN: 57880

European-Finnish (FIN) AF: 0.565 AC: 25983 AN: 46008

Middle Eastern (MID) AF: 0.665 AC: 2917 AN: 4386

European-Non Finnish (NFE) AF: 0.588 AC: 586679 AN: 997768

Other (OTH) AF: 0.570 AC: 29362 AN: 51498

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

African (AFR) AF: 0.226 AC: 9358 AN: 41468

American (AMR) AF: 0.618 AC: 9435 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2471 AN: 3470

East Asian (EAS) AF: 0.586 AC: 3026 AN: 5164

South Asian (SAS) AF: 0.553 AC: 2666 AN: 4824

European-Finnish (FIN) AF: 0.576 AC: 6053 AN: 10508

Middle Eastern (MID) AF: 0.597 AC: 172 AN: 288

European-Non Finnish (NFE) AF: 0.596 AC: 40511 AN: 67952

Other (OTH) AF: 0.560 AC: 1177 AN: 2102

Alfa AF: 0.532 Hom.: 3013

Bravo AF: 0.492

Asia WGS AF: 0.509 AC: 1764 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.16
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10839236; hg19: chr11-49192667;