rs560644274

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014334.4(FRRS1L):​c.-122C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 1,245,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 28)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

FRRS1L
NM_014334.4 upstream_gene

Scores

1
1
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

Publications

0 publications found
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 Gene-Disease associations (from GenCC):
  • developmental and epileptic encephalopathy, 37
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • autosomal recessive non-syndromic intellectual disability
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21279296).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014334.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
FRRS1L
NM_014334.4
MANE Select
c.-122C>T
upstream_gene
N/ANP_055149.3

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
FRRS1L
ENST00000561981.5
TSL:1 MANE Select
c.-122C>T
upstream_gene
N/AENSP00000477141.2

Frequencies

GnomAD3 genomes
AF:
0.00000664
AC:
1
AN:
150650
Hom.:
0
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.0000243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000129
AC:
1
AN:
77634
AF XY:
0.0000229
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000643
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000482
AC:
6
AN:
1245412
Hom.:
0
Cov.:
25
AF XY:
0.00000653
AC XY:
4
AN XY:
612886
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
25934
American (AMR)
AF:
0.0000393
AC:
1
AN:
25422
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19794
East Asian (EAS)
AF:
0.00
AC:
0
AN:
27284
South Asian (SAS)
AF:
0.0000162
AC:
1
AN:
61566
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
29812
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3454
European-Non Finnish (NFE)
AF:
0.00000399
AC:
4
AN:
1002140
Other (OTH)
AF:
0.00
AC:
0
AN:
50006
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000444247), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.300
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000664
AC:
1
AN:
150650
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
73482
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0000243
AC:
1
AN:
41178
American (AMR)
AF:
0.00
AC:
0
AN:
15168
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3440
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4968
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4804
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10290
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
310
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67504
Other (OTH)
AF:
0.00
AC:
0
AN:
2076
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.018
T
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.14
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.40
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L
PhyloP100
1.2
PrimateAI
Pathogenic
0.87
D
Sift4G
Benign
0.74
T
Polyphen
1.0
D
Vest4
0.24
MutPred
0.18
Loss of phosphorylation at S14 (P = 0.2239)
MVP
0.61
MPC
0.083
ClinPred
0.76
D
GERP RS
2.1
PromoterAI
0.25
Neutral
Varity_R
0.088
gMVP
0.13

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

Other links and lift over

dbSNP: rs560644274; hg19: chr9-111929540; API