rs2071010

Positions:

• chr11-72189920-G-A
• chr11-72189920-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLR1	NM_000802.3	c.-20G>A		5_prime_UTR_variant	1/5		NP_000793.1
FOLR1	NM_016724.3	c.-75+161G>A		intron_variant			NP_057936.1
FOLR1	NM_016725.3	c.-9+161G>A		intron_variant			NP_057937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOLR1	ENST00000312293.9	c.-9+161G>A		intron_variant		1		ENSP00000308137	P1
FOLR1	ENST00000393681.6	c.-75+161G>A		intron_variant		1		ENSP00000377286	P1
	ENST00000378140.3	n.419+8593C>T		intron_variant, non_coding_transcript_variant		3
FOLR1	ENST00000675784.1	c.-20G>A		5_prime_UTR_variant	1/5			ENSP00000502440	P1

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

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.0858

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.0610

Gnomad4 NFE AF: 0.0614

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0653 Hom.: 779

Bravo AF: 0.0550

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Gastrointestinal stromal tumor Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

Department of Pharmacy and Biotechnology, University of Bologna

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071010; hg19: chr11-71900964;