ENST00000393679.5:c.-24C>T

Variant names:

• chr11-72190626-C-T
• rs7109250
• ENST00000393679.5:c.-24C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000393679.5(FOLR1):​c.-24C>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 0.0385 in 152,216 control chromosomes in the GnomAD database, including 213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (213 hom., cov: 32)
  • Exomes 𝑓: 0.043 (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: -0.910
• Publications: 10 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=-0.85).
• BP6: Variant 11-72190626-C-T is Benign according to our data. Variant chr11-72190626-C-T is described in ClinVar as Benign. ClinVar VariationId is 1293890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

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_016724.3		c.-24C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_057936.1	P15328
	FOLR1	NM_016724.3		c.-24C>T		5_prime_UTR	Exon 2 of 6	NP_057936.1	P15328
	FOLR1	NM_000802.3		c.-9+695C>T		intron	N/A	NP_000793.1	P15328

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLR1	ENST00000393679.5	TSL:1	c.-24C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000377284.1	P15328
	FOLR1	ENST00000393681.6	TSL:1	c.-24C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000377286.2	P15328
	FOLR1	ENST00000393679.5	TSL:1	c.-24C>T		5_prime_UTR	Exon 1 of 5	ENSP00000377284.1	P15328

Frequencies

GnomAD3 genomes AF: 0.0384 AC: 5844 AN: 152050 Hom.: 211 Cov.: 32

Gnomad AFR AF: 0.0928

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0794

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00977

Gnomad OTH AF: 0.0321

GnomAD4 exome AF: 0.0435 AC: 2 AN: 46 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 2 AN XY: 32

African (AFR) AF: 0.00 AC: 0 AN: 2

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: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0263 AC: 1 AN: 38

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.0385 AC: 5851 AN: 152170 Hom.: 213 Cov.: 32 AF XY: 0.0395 AC XY: 2942 AN XY: 74400

African (AFR) AF: 0.0928 AC: 3848 AN: 41474

American (AMR) AF: 0.0198 AC: 302 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3472

East Asian (EAS) AF: 0.0794 AC: 411 AN: 5176

South Asian (SAS) AF: 0.0650 AC: 314 AN: 4832

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10598

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00979 AC: 666 AN: 68026

Other (OTH) AF: 0.0313 AC: 66 AN: 2112

Alfa AF: 0.0203 Hom.: 78

Bravo AF: 0.0412

Asia WGS AF: 0.0560 AC: 196 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	-0.85
CADD	Benign	5.9
DANN	Benign	0.76
PhyloP100		-0.91
PromoterAI		0.024	Neutral
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: rs7109250; hg19: chr11-71901670;