rs7926987

chr11-72138457-C-Gchr11-72138457-C-T

Variant summary

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

The NM_000804.4(FOLR3):c.169-504C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 152,220 control chromosomes in the GnomAD database, including 448 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 0.066 (448 hom., cov: 32)
• Consequence: FOLR3 NM_000804.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOLR3	NM_000804.4	c.169-504C>G		intron_variant		ENST00000611028.3
FOLR3	NR_178088.1	n.219-376C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOLR3	ENST00000611028.3	c.169-504C>G		intron_variant		1	NM_000804.4	P1
FOLR3	ENST00000612844.4	c.169-376C>G		intron_variant, NMD_transcript_variant		1
FOLR3	ENST00000546166.1	c.163-504C>G		intron_variant		3
FOLR3	ENST00000622388.4	c.169-504C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0662 AC: 10070 AN: 152102 Hom.: 447 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.0584

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

GnomAD4 genome AF: 0.0663 AC: 10085 AN: 152220 Hom.: 448 Cov.: 32 AF XY: 0.0679 AC XY: 5050 AN XY: 74418

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0360

Gnomad4 ASJ AF: 0.0481

Gnomad4 EAS AF: 0.0158

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0499

Gnomad4 OTH AF: 0.0588

Alfa AF: 0.0292 Hom.: 23

Bravo AF: 0.0623

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.16
Dann	Benign	0.39

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: rs7926987; hg19: chr11-71849503;