rs202719

Variant names:

• chr11-49171138-T-C
• rs202719
• NM_004476.3:c.1308+57A>G

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+57A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,478,334 control chromosomes in the GnomAD database, including 17,548 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 0.18 (2919 hom., cov: 31)
  • Exomes 𝑓: 0.14 (14629 hom.)
• Consequence: FOLH1 NM_004476.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLH1	NM_004476.3	MANE Select	c.1308+57A>G		intron	N/A	NP_004467.1	Q04609-1
	FOLH1	NM_001193471.3		c.1263+57A>G		intron	N/A	NP_001180400.1	Q04609-7
	FOLH1	NM_001014986.3		c.1308+57A>G		intron	N/A	NP_001014986.1	Q04609-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLH1	ENST00000256999.7	TSL:1 MANE Select	c.1308+57A>G		intron	N/A	ENSP00000256999.2	Q04609-1
	FOLH1	ENST00000340334.11	TSL:1	c.1263+57A>G		intron	N/A	ENSP00000344131.7	Q04609-7
	FOLH1	ENST00000356696.7	TSL:1	c.1308+57A>G		intron	N/A	ENSP00000349129.3	Q04609-8

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27570 AN: 151938 Hom.: 2918 Cov.: 31

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.144 AC: 191381 AN: 1326278 Hom.: 14629 AF XY: 0.143 AC XY: 93822 AN XY: 655474

African (AFR) AF: 0.285 AC: 8053 AN: 28290

American (AMR) AF: 0.131 AC: 4009 AN: 30568

Ashkenazi Jewish (ASJ) AF: 0.0939 AC: 2083 AN: 22192

East Asian (EAS) AF: 0.154 AC: 5562 AN: 36118

South Asian (SAS) AF: 0.131 AC: 8222 AN: 62912

European-Finnish (FIN) AF: 0.207 AC: 9939 AN: 48088

Middle Eastern (MID) AF: 0.108 AC: 520 AN: 4826

European-Non Finnish (NFE) AF: 0.140 AC: 145527 AN: 1039396

Other (OTH) AF: 0.139 AC: 7466 AN: 53888

GnomAD4 genome AF: 0.181 AC: 27579 AN: 152056 Hom.: 2919 Cov.: 31 AF XY: 0.184 AC XY: 13676 AN XY: 74312

African (AFR) AF: 0.282 AC: 11681 AN: 41480

American (AMR) AF: 0.133 AC: 2026 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 348 AN: 3468

East Asian (EAS) AF: 0.158 AC: 817 AN: 5168

South Asian (SAS) AF: 0.122 AC: 590 AN: 4826

European-Finnish (FIN) AF: 0.227 AC: 2389 AN: 10544

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.137 AC: 9291 AN: 67982

Other (OTH) AF: 0.143 AC: 301 AN: 2104

Alfa AF: 0.161 Hom.: 304

Bravo AF: 0.179

Asia WGS AF: 0.128 AC: 442 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.83
DANN	Benign	0.83
PhyloP100		-0.97
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: rs202719; hg19: chr11-49192690; COSMIC: COSV57051356;