rs7925545

Positions:

• chr11-72134495-A-G

Variant summary

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

The ENST00000622388.4(FOLR3):​c.-6-1452A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 152,268 control chromosomes in the GnomAD database, including 738 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 0.081 (738 hom., cov: 32)
• Consequence: FOLR3 ENST00000622388.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

Genes affected

FOLR3 (HGNC:3795): (folate receptor gamma) This gene encodes a member of the folate receptor (FOLR) family of proteins, which have a high affinity for folic acid and for several reduced folic acid derivatives, and mediate delivery of 5-methyltetrahydrofolate to the interior of cells. Expression of this gene may be elevated in ovarian and primary peritoneal carcinoma. This gene is present in a gene cluster on chromosome 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOLR3	ENST00000622388.4	c.-6-1452A>G		intron_variant		5		ENSP00000481833

Frequencies

GnomAD3 genomes AF: 0.0807 AC: 12275 AN: 152150 Hom.: 731 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0410

Gnomad ASJ AF: 0.0482

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0664

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

GnomAD4 genome AF: 0.0808 AC: 12309 AN: 152268 Hom.: 738 Cov.: 32 AF XY: 0.0820 AC XY: 6102 AN XY: 74444

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0409

Gnomad4 ASJ AF: 0.0482

Gnomad4 EAS AF: 0.0158

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.0666

Alfa AF: 0.0507 Hom.: 459

Bravo AF: 0.0786

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.3
DANN	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7925545; hg19: chr11-71845541;