11-72190534-C-T

Position:

• chr11-72190534-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000393679.5(FOLR1):​c.-116C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 152,190 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (68 hom., cov: 32)
  • Exomes 𝑓: 0.026 (0 hom.)
• Consequence: FOLR1 ENST00000393679.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.29

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-72190534-C-T is Benign according to our data. Variant chr11-72190534-C-T is described in ClinVar as [Benign]. Clinvar id is 1232499.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 = 0.0259 (3946/152152) while in subpopulation AFR AF= 0.0506 (2101/41490). AF 95% confidence interval is 0.0488. There are 68 homozygotes in gnomad4. There are 1846 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 68 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLR1	NM_000802.3	c.-9+603C>T		intron_variant			NP_000793.1
FOLR1	NM_016724.3	c.-74-42C>T		intron_variant			NP_057936.1
FOLR1	NM_016725.3	c.-9+775C>T		intron_variant			NP_057937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000378140.3	n.419+7979G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3946 AN: 152034 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.0507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.00577

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.00642

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0179

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.0263 AC: 1 AN: 38 Hom.: 0 Cov.: 0 AF XY: 0.0278 AC XY: 1 AN XY: 36

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0333

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0259 AC: 3946 AN: 152152 Hom.: 68 Cov.: 32 AF XY: 0.0248 AC XY: 1846 AN XY: 74376

Gnomad4 AFR AF: 0.0506

Gnomad4 AMR AF: 0.0151

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.00579

Gnomad4 SAS AF: 0.0340

Gnomad4 FIN AF: 0.00642

Gnomad4 NFE AF: 0.0179

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0214 Hom.: 5

Bravo AF: 0.0275

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9282688; hg19: chr11-71901578;