11-72190084-G-A

Position:

• chr11-72190084-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000312293.9(FOLR1):​c.-9+325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 152,410 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (123 hom., cov: 32)
  • Exomes 𝑓: 0.053 (0 hom.)
• Consequence: FOLR1 ENST00000312293.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.47

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-72190084-G-A is Benign according to our data. Variant chr11-72190084-G-A is described in ClinVar as [Benign]. Clinvar id is 1252638.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0344 (5242/152296) while in subpopulation NFE AF= 0.0417 (2835/68026). AF 95% confidence interval is 0.0404. There are 123 homozygotes in gnomad4. There are 2731 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 123 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLR1	NM_000802.3	c.-9+153G>A		intron_variant			NP_000793.1
FOLR1	NM_016724.3	c.-75+325G>A		intron_variant			NP_057936.1
FOLR1	NM_016725.3	c.-9+325G>A		intron_variant			NP_057937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOLR1	ENST00000312293.9	c.-9+325G>A		intron_variant		1		ENSP00000308137	P1
FOLR1	ENST00000393681.6	c.-75+325G>A		intron_variant		1		ENSP00000377286	P1
	ENST00000378140.3	n.419+8429C>T		intron_variant, non_coding_transcript_variant		3
FOLR1	ENST00000675784.1	c.-9+153G>A		intron_variant				ENSP00000502440	P1

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5242 AN: 152178 Hom.: 123 Cov.: 32

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0177

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0417

Gnomad OTH AF: 0.0301

GnomAD4 exome AF: 0.0526 AC: 6 AN: 114 Hom.: 0 AF XY: 0.0500 AC XY: 4 AN XY: 80

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.0417

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.0344 AC: 5242 AN: 152296 Hom.: 123 Cov.: 32 AF XY: 0.0367 AC XY: 2731 AN XY: 74462

Gnomad4 AFR AF: 0.0189

Gnomad4 AMR AF: 0.0177

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.0199

Gnomad4 SAS AF: 0.0128

Gnomad4 FIN AF: 0.0937

Gnomad4 NFE AF: 0.0417

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0471 Hom.: 29

Bravo AF: 0.0282

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.9
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs117787264; hg19: chr11-71901128;