ENST00000312293.9:c.-9+1042A>C

Variant names:

• chr11-72190801-A-C
• rs7125189
• ENST00000312293.9:c.-9+1042A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000312293.9(FOLR1):​c.-9+1042A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 152,266 control chromosomes in the GnomAD database, including 250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.041 (250 hom., cov: 32)
• Consequence: FOLR1 ENST00000312293.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.33
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 11-72190801-A-C is Benign according to our data. Variant chr11-72190801-A-C is described in ClinVar as Benign. ClinVar VariationId is 1236976.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0987 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000312293.9. 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+870A>C		intron	N/A	NP_000793.1	P15328
	FOLR1	NM_016724.3		c.-9+160A>C		intron	N/A	NP_057936.1	P15328
	FOLR1	NM_016725.3		c.-9+1042A>C		intron	N/A	NP_057937.1	P15328

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLR1	ENST00000312293.9	TSL:1	c.-9+1042A>C		intron	N/A	ENSP00000308137.4	P15328
	FOLR1	ENST00000393679.5	TSL:1	c.-9+160A>C		intron	N/A	ENSP00000377284.1	P15328
	FOLR1	ENST00000393681.6	TSL:1	c.-9+160A>C		intron	N/A	ENSP00000377286.2	P15328

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6200 AN: 152148 Hom.: 248 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00966

Gnomad OTH AF: 0.0325

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

GnomAD4 genome AF: 0.0408 AC: 6207 AN: 152266 Hom.: 250 Cov.: 32 AF XY: 0.0419 AC XY: 3119 AN XY: 74448

African (AFR) AF: 0.101 AC: 4206 AN: 41560

American (AMR) AF: 0.0203 AC: 311 AN: 15296

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

East Asian (EAS) AF: 0.0791 AC: 409 AN: 5170

South Asian (SAS) AF: 0.0648 AC: 313 AN: 4828

European-Finnish (FIN) AF: 0.0135 AC: 143 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00968 AC: 658 AN: 68006

Other (OTH) AF: 0.0317 AC: 67 AN: 2112

Alfa AF: 0.0224 Hom.: 45

Bravo AF: 0.0437

Asia WGS AF: 0.0570 AC: 197 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.25
DANN	Benign	0.45
PhyloP100		-3.3
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: rs7125189; hg19: chr11-71901845;