11-126269044-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The ENST00000532125(FOXRED1):​c.-163G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00069 in 746,570 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

FOXRED1
ENST00000532125 5_prime_UTR

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -1.23
Variant links:
Genes affected
FOXRED1 (HGNC:26927): (FAD dependent oxidoreductase domain containing 1) This gene encodes a protein that contains a FAD-dependent oxidoreductase domain. The encoded protein is localized to the mitochondria and may function as a chaperone protein required for the function of mitochondrial complex I. Mutations in this gene are associated with mitochondrial complex I deficiency. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]
SRPRA (HGNC:11307): (SRP receptor subunit alpha) The gene encodes a subunit of the endoplasmic reticulum signal recognition particle receptor that, in conjunction with the signal recognition particle, is involved in the targeting and translocation of signal sequence tagged secretory and membrane proteins across the endoplasmic reticulum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 11-126269044-G-C is Benign according to our data. Variant chr11-126269044-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 303531.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00233 (355/152392) while in subpopulation AFR AF= 0.00817 (340/41602). AF 95% confidence interval is 0.00746. There are 3 homozygotes in gnomad4. There are 165 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOXRED1ENST00000692336 linkc.-163G>C 5_prime_UTR_variant Exon 1 of 11 ENSP00000508540.1 A0A8I5KTW5
FOXRED1ENST00000532125 linkc.-163G>C 5_prime_UTR_variant Exon 1 of 11 2 ENSP00000434178.2 A0A8J9AK24
FOXRED1ENST00000685484 linkc.-163G>C 5_prime_UTR_variant Exon 1 of 10 ENSP00000510622.1 A0A8I5KUS8

Frequencies

GnomAD3 genomes
AF:
0.00234
AC:
356
AN:
152274
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00822
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000719
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:
0.0000147
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000503
AC:
63
AN:
125152
Hom.:
0
AF XY:
0.000357
AC XY:
24
AN XY:
67308
show subpopulations
Gnomad AFR exome
AF:
0.00841
Gnomad AMR exome
AF:
0.000344
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.000269
AC:
160
AN:
594178
Hom.:
0
Cov.:
7
AF XY:
0.000202
AC XY:
64
AN XY:
317510
show subpopulations
Gnomad4 AFR exome
AF:
0.00732
Gnomad4 AMR exome
AF:
0.000478
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000111
Gnomad4 OTH exome
AF:
0.000568
GnomAD4 genome
AF:
0.00233
AC:
355
AN:
152392
Hom.:
3
Cov.:
33
AF XY:
0.00221
AC XY:
165
AN XY:
74518
show subpopulations
Gnomad4 AFR
AF:
0.00817
Gnomad4 AMR
AF:
0.000718
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00145
Hom.:
0
Bravo
AF:
0.00268
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Mitochondrial complex I deficiency, nuclear type 1 Uncertain:1
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided Benign:1
Aug 22, 2020
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
1.4
DANN
Benign
0.47

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.

Other links and lift over

dbSNP: rs552937899; hg19: chr11-126138939; API