Variant rs527415212 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The 9-109167291-T-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,309,664 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00069 ( 4 hom., cov: 28)

Exomes 𝑓: 0.0012 ( 41 hom. )

Consequence

FRRS1L
NM_014334.4 upstream_gene

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.941

Variant links:

Genes affected

FRRS1L (HGNC:1362): (ferric chelate reductase 1 like) This gene encodes a component of the outer-core of an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor protein in the brain. The encoded protein is thought to interact with inner-core components of the receptor, and play a role in the modulation of glutamate signaling. Mutations in this gene are associated with early infantile epileptic encephalopathy 37. [provided by RefSeq, Jul 2016]

FRRS1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005487889).

BP6

Variant 9-109167291-T-A is Benign according to our data. Variant chr9-109167291-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 476299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000685 (103/150334) while in subpopulation SAS AF= 0.021 (100/4762). AF 95% confidence interval is 0.0177. There are 4 homozygotes in gnomad4. There are 73 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRRS1L	NM_014334.4 linkuse as main transcript			upstream_gene_variant		ENST00000561981.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRRS1L	ENST00000561981.5 linkuse as main transcript			upstream_gene_variant		1	NM_014334.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000686

AC:

103

AN:

150234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0210

Gnomad FIN

AF:

0.0000972

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000484

GnomAD3 exomes

AF:

0.00392

AC:

219

AN:

55826

Hom.:

AF XY:

0.00581

AC XY:

183

AN XY:

31504

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000197

Gnomad ASJ exome

AF:

0.000415

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0292

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000755

Gnomad OTH exome

AF:

0.00224

GnomAD4 exome

AF:

0.00121

AC:

1404

AN:

1159330

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

1011

AN XY:

569768

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000105

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000447

Gnomad4 SAS exome

AF:

0.0232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000589

Gnomad4 OTH exome

AF:

0.00156

GnomAD4 genome

AF:

0.000685

AC:

103

AN:

150334

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

73416

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0210

Gnomad4 FIN

AF:

0.0000972

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000277

Hom.:

Bravo

AF:

0.000159

ExAC

AF:

0.00215

AC:

234

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

FRRS1L-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 03, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 13, 2021

- -

Developmental and epileptic encephalopathy, 37

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.017

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.53

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.0055

MetaSVM

Benign

-1.0

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.67

MutPred

0.56

Loss of methylation at R5 (P = 0.1472);

MVP

0.40

ClinPred

0.031

GERP RS

-0.15

Varity_R

0.24

gMVP

0.13

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over