11-72195454-C-A

Variant names:

• chr11-72195454-C-A
• rs121918405
• NM_016729.3:c.352C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016729.3(FOLR1):​c.352C>A​(p.Gln118Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FOLR1 NM_016729.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

Genes affected

FOLR1 (HGNC:3791): (folate receptor alpha) The protein encoded by this gene is a member of the folate receptor family. Members of this gene family bind folic acid and its reduced derivatives, and transport 5-methyltetrahydrofolate into cells. This gene product is a secreted protein that either anchors to membranes via a glycosyl-phosphatidylinositol linkage or exists in a soluble form. Mutations in this gene have been associated with neurodegeneration due to cerebral folate transport deficiency. Due to the presence of two promoters, multiple transcription start sites, and alternative splicing, multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Oct 2009]

ENSG00000204971 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOLR1	NM_016729.3	c.352C>A	p.Gln118Lys	missense_variant	Exon 2 of 4	ENST00000393676.5	NP_057941.1
FOLR1	NM_000802.3	c.352C>A	p.Gln118Lys	missense_variant	Exon 3 of 5		NP_000793.1
FOLR1	NM_016724.3	c.352C>A	p.Gln118Lys	missense_variant	Exon 4 of 6		NP_057936.1
FOLR1	NM_016725.3	c.352C>A	p.Gln118Lys	missense_variant	Exon 3 of 5		NP_057937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOLR1	ENST00000393676.5	c.352C>A	p.Gln118Lys	missense_variant	Exon 2 of 4	1	NM_016729.3	ENSP00000377281.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T;T;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.56	.;.;.;T
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Uncertain	-0.098	T
MutationAssessor	Pathogenic	3.5	H;H;H;H
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.5	N;N;N;N
REVEL	Uncertain	0.51
Sift	Benign	0.14	T;T;T;T
Sift4G	Benign	0.093	T;T;T;T
Polyphen		0.76	P;P;P;P
Vest4		0.28
MutPred		0.58		Gain of methylation at Q118 (P = 0.0106);Gain of methylation at Q118 (P = 0.0106);Gain of methylation at Q118 (P = 0.0106);Gain of methylation at Q118 (P = 0.0106);
MVP		0.87
MPC		0.56
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.42
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs121918405; hg19: chr11-71906498;