rs514933

Positions:

• chr11-72219163-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000803.5(FOLR2):​c.150+429T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,858 control chromosomes in the GnomAD database, including 16,166 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (16166 hom., cov: 31)
• Consequence: FOLR2 NM_000803.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830

Genes affected

FOLR2 (HGNC:3793): (folate receptor beta) The protein encoded by this gene is a member of the folate receptor (FOLR) family, and these genes exist in a cluster on chromosome 11. Members of this gene family have a high affinity for folic acid and for several reduced folic acid derivatives, and they mediate delivery of 5-methyltetrahydrofolate to the interior of cells. This protein has a 68% and 79% sequence homology with the FOLR1 and FOLR3 proteins, respectively. Although this protein was originally thought to be specific to placenta, it can also exist in other tissues, and it may play a role in the transport of methotrexate in synovial macrophages in rheumatoid arthritis patients. Multiple transcript variants that encode the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLR2	NM_000803.5	c.150+429T>C		intron_variant		ENST00000298223.11	NP_000794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOLR2	ENST00000298223.11	c.150+429T>C		intron_variant		1	NM_000803.5	ENSP00000298223	P1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67329 AN: 151740 Hom.: 16124 Cov.: 31

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.444 AC: 67426 AN: 151858 Hom.: 16166 Cov.: 31 AF XY: 0.444 AC XY: 32920 AN XY: 74188

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.431

Alfa AF: 0.385 Hom.: 13302

Bravo AF: 0.442

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.69
DANN	Benign	0.57

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: rs514933; hg19: chr11-71930207;