11-72219163-T-C

Variant names:

• chr11-72219163-T-C
• rs514933
• NM_000803.5:c.150+429T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000803.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLR2	NM_000803.5	MANE Select	c.150+429T>C		intron	N/A	NP_000794.3	P14207
	FOLR2	NM_001113534.2		c.150+429T>C		intron	N/A	NP_001107006.1	P14207
	FOLR2	NM_001113535.2		c.150+429T>C		intron	N/A	NP_001107007.1	P14207

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLR2	ENST00000298223.11	TSL:1 MANE Select	c.150+429T>C		intron	N/A	ENSP00000298223.6	P14207
	FOLR2	ENST00000868542.1		c.150+429T>C		intron	N/A	ENSP00000538601.1
	FOLR2	ENST00000868543.1		c.150+429T>C		intron	N/A	ENSP00000538602.1

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

African (AFR) AF: 0.639 AC: 26480 AN: 41410

American (AMR) AF: 0.302 AC: 4617 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1787 AN: 3464

East Asian (EAS) AF: 0.291 AC: 1496 AN: 5146

South Asian (SAS) AF: 0.373 AC: 1798 AN: 4820

European-Finnish (FIN) AF: 0.424 AC: 4458 AN: 10522

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25426 AN: 67932

Other (OTH) AF: 0.431 AC: 903 AN: 2096

Alfa AF: 0.391 Hom.: 17806

Bravo AF: 0.442

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.69
DANN	Benign	0.57
PhyloP100		-0.083
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs514933; hg19: chr11-71930207;