11-72190801-A-C

Position:

• chr11-72190801-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000312293.9(FOLR1):​c.-9+1042A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 152,266 control chromosomes in the GnomAD database, including 250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.041 (250 hom., cov: 32)
• Consequence: FOLR1 ENST00000312293.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.33

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=-0.97).
• BP6: Variant 11-72190801-A-C is Benign according to our data. Variant chr11-72190801-A-C is described in ClinVar as [Benign]. Clinvar id is 1236976.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOLR1	NM_000802.3	c.-9+870A>C		intron_variant
FOLR1	NM_016724.3	c.-9+160A>C		intron_variant
FOLR1	NM_016725.3	c.-9+1042A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000378140.3	n.419+7712T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6200 AN: 152148 Hom.: 248 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00966

Gnomad OTH AF: 0.0325

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

GnomAD4 genome AF: 0.0408 AC: 6207 AN: 152266 Hom.: 250 Cov.: 32 AF XY: 0.0419 AC XY: 3119 AN XY: 74448

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0203

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.0791

Gnomad4 SAS AF: 0.0648

Gnomad4 FIN AF: 0.0135

Gnomad4 NFE AF: 0.00968

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0228 Hom.: 40

Bravo AF: 0.0437

Asia WGS AF: 0.0570 AC: 197 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

May 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.25
DANN	Benign	0.45

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: rs7125189; hg19: chr11-71901845;