ENST00000312293.9:c.-9+161G>A

Variant names:

• chr11-72189920-G-A
• rs2071010
• ENST00000312293.9:c.-9+161G>A

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+161G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 152,268 control chromosomes in the GnomAD database, including 389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.058 (389 hom., cov: 32)
• Consequence: FOLR1 ENST00000312293.9 intron
• Clinical Significance: Benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 1.46
• Publications: 26 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: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen

ENSG00000204971 (HGNC:58347):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-72189920-G-A is Benign according to our data. Variant chr11-72189920-G-A is described in ClinVar as Benign. ClinVar VariationId is 157589.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.164 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.-20G>A		5_prime_UTR	Exon 1 of 5	NP_000793.1	P15328
	FOLR1	NM_016724.3		c.-75+161G>A		intron	N/A	NP_057936.1	P15328
	FOLR1	NM_016725.3		c.-9+161G>A		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+161G>A		intron	N/A	ENSP00000308137.4	P15328
	FOLR1	ENST00000393681.6	TSL:1	c.-75+161G>A		intron	N/A	ENSP00000377286.2	P15328
	FOLR1	ENST00000675784.1		c.-20G>A		5_prime_UTR	Exon 1 of 5	ENSP00000502440.1	P15328

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8783 AN: 152150 Hom.: 386 Cov.: 32

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.0860

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0610

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0614

Gnomad OTH AF: 0.0535

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

GnomAD4 genome AF: 0.0577 AC: 8792 AN: 152268 Hom.: 389 Cov.: 32 AF XY: 0.0621 AC XY: 4619 AN XY: 74436

African (AFR) AF: 0.0142 AC: 592 AN: 41582

American (AMR) AF: 0.0858 AC: 1312 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3470

East Asian (EAS) AF: 0.173 AC: 899 AN: 5182

South Asian (SAS) AF: 0.167 AC: 804 AN: 4820

European-Finnish (FIN) AF: 0.0610 AC: 647 AN: 10608

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0614 AC: 4175 AN: 68004

Other (OTH) AF: 0.0610 AC: 129 AN: 2114

Alfa AF: 0.0625 Hom.: 1161

Bravo AF: 0.0550

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Gastrointestinal stromal tumor (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.56
PhyloP100		1.5
PromoterAI		-0.0048	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs2071010; hg19: chr11-71900964;