rs651646

Positions:

• chr11-72218482-T-A
• chr11-72218482-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.-24-79T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,294,736 control chromosomes in the GnomAD database, including 142,819 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 0.52 (21364 hom., cov: 31)
  • Exomes 𝑓: 0.46 (121455 hom.)
• Consequence: FOLR2 NM_000803.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLR2	NM_000803.5	c.-24-79T>A		intron_variant		ENST00000298223.11	NP_000794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOLR2	ENST00000298223.11	c.-24-79T>A		intron_variant		1	NM_000803.5	ENSP00000298223.6

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78409 AN: 151772 Hom.: 21318 Cov.: 31

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.491

GnomAD4 exome AF: 0.456 AC: 521210 AN: 1142846 Hom.: 121455 AF XY: 0.459 AC XY: 262939 AN XY: 573414

Gnomad4 AFR exome AF: 0.707

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.557

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.539

Gnomad4 FIN exome AF: 0.501

Gnomad4 NFE exome AF: 0.441

Gnomad4 OTH exome AF: 0.473

GnomAD4 genome AF: 0.517 AC: 78513 AN: 151890 Hom.: 21364 Cov.: 31 AF XY: 0.521 AC XY: 38670 AN XY: 74234

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.497

Alfa AF: 0.347 Hom.: 916

Bravo AF: 0.511

Asia WGS AF: 0.559 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.078
DANN	Benign	0.82

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: rs651646; hg19: chr11-71929526;