11-72190447-G-A

Position:

• chr11-72190447-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000393679.5(FOLR1):​c.-203G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 152,272 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (206 hom., cov: 32)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: FOLR1 ENST00000393679.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0800

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-72190447-G-A is Benign according to our data. Variant chr11-72190447-G-A is described in ClinVar as [Benign]. Clinvar id is 1296043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLR1	NM_000802.3	c.-9+516G>A		intron_variant			NP_000793.1
FOLR1	NM_016724.3	c.-74-129G>A		intron_variant			NP_057936.1
FOLR1	NM_016725.3	c.-9+688G>A		intron_variant			NP_057937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000378140.3	n.419+8066C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 5812 AN: 152106 Hom.: 204 Cov.: 32

Gnomad AFR AF: 0.0924

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0790

Gnomad SAS AF: 0.0648

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00960

Gnomad OTH AF: 0.0312

GnomAD4 exome AF: 0.0417 AC: 2 AN: 48 Hom.: 0 Cov.: 0 AF XY: 0.0500 AC XY: 2 AN XY: 40

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0526

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0382 AC: 5819 AN: 152224 Hom.: 206 Cov.: 32 AF XY: 0.0393 AC XY: 2923 AN XY: 74434

Gnomad4 AFR AF: 0.0924

Gnomad4 AMR AF: 0.0197

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.0790

Gnomad4 SAS AF: 0.0646

Gnomad4 FIN AF: 0.0135

Gnomad4 NFE AF: 0.00961

Gnomad4 OTH AF: 0.0304

Alfa AF: 0.0172 Hom.: 46

Bravo AF: 0.0408

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 24, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs1540087; hg19: chr11-71901491;