Variant 11-72190084-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000312293.9(FOLR1):c.-9+325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 152,410 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.034 ( 123 hom., cov: 32)

Exomes 𝑓: 0.053 ( 0 hom. )

Consequence

FOLR1
ENST00000312293.9 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.47

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 11-72190084-G-A is Benign according to our data. Variant chr11-72190084-G-A is described in ClinVar as [Benign]. Clinvar id is 1252638.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0344 (5242/152296) while in subpopulation NFE AF= 0.0417 (2835/68026). AF 95% confidence interval is 0.0404. There are 123 homozygotes in gnomad4. There are 2731 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 123 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect
FOLR1	NM_000802.3 linkuse as main transcript	c.-9+153G>A	intron_variant
FOLR1	NM_016724.3 linkuse as main transcript	c.-75+325G>A	intron_variant
FOLR1	NM_016725.3 linkuse as main transcript	c.-9+325G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Appris
FOLR1	ENST00000312293.9 linkuse as main transcript	c.-9+325G>A	intron_variant	1	P1
FOLR1	ENST00000393681.6 linkuse as main transcript	c.-75+325G>A	intron_variant	1	P1
	ENST00000378140.3 linkuse as main transcript	n.419+8429C>T	intron_variant, non_coding_transcript_variant	3
FOLR1	ENST00000675784.1 linkuse as main transcript	c.-9+153G>A	intron_variant		P1

Frequencies

GnomAD3 genomes

AF:

0.0344

AC:

5242

AN:

152178

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0189

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.0177

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.0198

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0937

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0417

Gnomad OTH

AF:

0.0301

GnomAD4 exome

AF:

0.0526

AC:

AN:

114

Hom.:

AF XY:

0.0500

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.0417

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.0344

AC:

5242

AN:

152296

Hom.:

123

Cov.:

AF XY:

0.0367

AC XY:

2731

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0189

Gnomad4 AMR

AF:

0.0177

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.0199

Gnomad4 SAS

AF:

0.0128

Gnomad4 FIN

AF:

0.0937

Gnomad4 NFE

AF:

0.0417

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0471

Hom.:

Bravo

AF:

0.0282

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.9

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over