ENST00000393679.5:c.-116C>T

Variant names:

• chr11-72190534-C-T
• rs9282688
• ENST00000393679.5:c.-116C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000393679.5(FOLR1):​c.-116C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 152,190 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (68 hom., cov: 32)
  • Exomes 𝑓: 0.026 (0 hom.)
• Consequence: FOLR1 ENST00000393679.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.29
• Publications: 3 publications found

Genes affected

FOLR1 (HGNC:3791): (folate receptor alpha) The protein encoded by this gene is a member of the folate receptor family. Members of this gene family bind folic acid and its reduced derivatives, and transport 5-methyltetrahydrofolate into cells. This gene product is a secreted protein that either anchors to membranes via a glycosyl-phosphatidylinositol linkage or exists in a soluble form. Mutations in this gene have been associated with neurodegeneration due to cerebral folate transport deficiency. Due to the presence of two promoters, multiple transcription start sites, and alternative splicing, multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Oct 2009]

FOLR1 Gene-Disease associations (from GenCC):

• neurodegenerative syndrome due to cerebral folate transport deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ENSG00000204971 (HGNC:58347):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-72190534-C-T is Benign according to our data. Variant chr11-72190534-C-T is described in ClinVar as Benign. ClinVar VariationId is 1232499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0259 (3946/152152) while in subpopulation AFR AF = 0.0506 (2101/41490). AF 95% confidence interval is 0.0488. There are 68 homozygotes in GnomAd4. There are 1846 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 68 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393679.5. 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
	FOLR1	NM_000802.3		c.-9+603C>T		intron	N/A	NP_000793.1	P15328
	FOLR1	NM_016724.3		c.-74-42C>T		intron	N/A	NP_057936.1	P15328
	FOLR1	NM_016725.3		c.-9+775C>T		intron	N/A	NP_057937.1	P15328

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLR1	ENST00000393679.5	TSL:1	c.-116C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000377284.1	P15328
	FOLR1	ENST00000393679.5	TSL:1	c.-116C>T		5_prime_UTR	Exon 1 of 5	ENSP00000377284.1	P15328
	FOLR1	ENST00000312293.9	TSL:1	c.-9+775C>T		intron	N/A	ENSP00000308137.4	P15328

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3946 AN: 152034 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.0507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.00577

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.00642

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0179

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.0263 AC: 1 AN: 38 Hom.: 0 Cov.: 0 AF XY: 0.0278 AC XY: 1 AN XY: 36

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0333 AC: 1 AN: 30

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0259 AC: 3946 AN: 152152 Hom.: 68 Cov.: 32 AF XY: 0.0248 AC XY: 1846 AN XY: 74376

African (AFR) AF: 0.0506 AC: 2101 AN: 41490

American (AMR) AF: 0.0151 AC: 230 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3470

East Asian (EAS) AF: 0.00579 AC: 30 AN: 5184

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4824

European-Finnish (FIN) AF: 0.00642 AC: 68 AN: 10584

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.0179 AC: 1215 AN: 68020

Other (OTH) AF: 0.0199 AC: 42 AN: 2108

Alfa AF: 0.0220 Hom.: 7

Bravo AF: 0.0275

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.68
PhyloP100		-1.3
PromoterAI		-0.016	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9282688; hg19: chr11-71901578;