11-72221370-T-C

Position:

• chr11-72221370-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.475+59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,600,206 control chromosomes in the GnomAD database, including 40,465 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 0.27 (6466 hom., cov: 31)
  • Exomes 𝑓: 0.21 (33999 hom.)
• Consequence: FOLR2 NM_000803.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLR2	NM_000803.5	c.475+59T>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.475+59T>C		intron_variant		1	NM_000803.5	ENSP00000298223.6

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40624 AN: 151856 Hom.: 6457 Cov.: 31

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.206 AC: 298960 AN: 1448232 Hom.: 33999 Cov.: 35 AF XY: 0.210 AC XY: 151047 AN XY: 718588

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.331

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.268 AC: 40668 AN: 151974 Hom.: 6466 Cov.: 31 AF XY: 0.271 AC XY: 20174 AN XY: 74306

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.230

Alfa AF: 0.203 Hom.: 3509

Bravo AF: 0.273

Asia WGS AF: 0.400 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.59
DANN	Benign	0.43

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: rs2298444; hg19: chr11-71932414; COSMIC: COSV53351833; COSMIC: COSV53351833;