rs188821779

Variant names:

• chr11-72139116-G-C
• rs188821779
• NM_000804.4:c.324G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-72139116-G-C
• chr11-72139116-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000804.4(FOLR3):​c.324G>C​(p.Glu108Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00121 in 1,613,886 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E108Q) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0065 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (12 hom.)
• Consequence: FOLR3 NM_000804.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.83
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011602581).
• BP6: Variant 11-72139116-G-C is Benign according to our data. Variant chr11-72139116-G-C is described in ClinVar as Benign. ClinVar VariationId is 711557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00648 (987/152330) while in subpopulation AFR AF = 0.0223 (925/41566). AF 95% confidence interval is 0.0211. There are 15 homozygotes in GnomAd4. There are 461 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000804.4. 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
	FOLR3	NM_000804.4	MANE Select	c.324G>C	p.Glu108Asp	missense	Exon 3 of 5	NP_000795.2	P41439-1
	FOLR3	NR_178088.1		n.502G>C		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLR3	ENST00000611028.3	TSL:1 MANE Select	c.324G>C	p.Glu108Asp	missense	Exon 3 of 5	ENSP00000481114.1	P41439-1
	FOLR3	ENST00000612844.4	TSL:1	n.452G>C		non_coding_transcript_exon	Exon 3 of 5	ENSP00000481027.1	P41439-4
	FOLR3	ENST00000897859.1		c.324G>C	p.Glu108Asp	missense	Exon 3 of 5	ENSP00000567918.1

Frequencies

GnomAD3 genomes AF: 0.00646 AC: 983 AN: 152212 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00159 AC: 397 AN: 250462 AF XY: 0.00122

Gnomad AFR exome AF: 0.0225

Gnomad AMR exome AF: 0.000897

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000663 AC: 969 AN: 1461556 Hom.: 12 Cov.: 34 AF XY: 0.000565 AC XY: 411 AN XY: 727064

African (AFR) AF: 0.0237 AC: 794 AN: 33480

American (AMR) AF: 0.00116 AC: 52 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111770

Other (OTH) AF: 0.00157 AC: 95 AN: 60368

GnomAD4 genome AF: 0.00648 AC: 987 AN: 152330 Hom.: 15 Cov.: 32 AF XY: 0.00619 AC XY: 461 AN XY: 74492

African (AFR) AF: 0.0223 AC: 925 AN: 41566

American (AMR) AF: 0.00314 AC: 48 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68022

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00183 Hom.: 2

Bravo AF: 0.00683

ExAC AF: 0.00191 AC: 232

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Pathogenic	0.17
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.41	T
PhyloP100		4.8
PrimateAI	Benign	0.48	T
Sift4G	Uncertain	0.0060	D
Vest4		0.70
MVP		0.33
ClinPred		0.027	T
GERP RS		2.3
gMVP		0.81
Mutation Taster		=85/15	polymorphism

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: rs188821779; hg19: chr11-71850160;