chr1-161766419-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_007348.4(ATF6):c.59T>C(p.Phe20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,613,306 control chromosomes in the GnomAD database, including 247 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.010 ( 8 hom., cov: 32)
Exomes 𝑓: 0.016 ( 239 hom. )
Consequence
ATF6
NM_007348.4 missense
NM_007348.4 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: 1.08
Genes affected
ATF6 (HGNC:791): (activating transcription factor 6) This gene encodes a transcription factor that activates target genes for the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Although it is a transcription factor, this protein is unusual in that it is synthesized as a transmembrane protein that is embedded in the ER. It functions as an ER stress sensor/transducer, and following ER stress-induced proteolysis, it functions as a nuclear transcription factor via a cis-acting ER stress response element (ERSE) that is present in the promoters of genes encoding ER chaperones. This protein has been identified as a survival factor for quiescent but not proliferative squamous carcinoma cells. There have been conflicting reports about the association of polymorphisms in this gene with diabetes in different populations, but another polymorphism has been associated with increased plasma cholesterol levels. This gene is also thought to be a potential therapeutic target for cystic fibrosis. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0039719343).
BP6
?
Variant 1-161766419-T-C is Benign according to our data. Variant chr1-161766419-T-C is described in ClinVar as [Benign]. Clinvar id is 1170814.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.01 (1528/152276) while in subpopulation SAS AF= 0.0174 (84/4824). AF 95% confidence interval is 0.0157. There are 8 homozygotes in gnomad4. There are 692 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATF6 | NM_007348.4 | c.59T>C | p.Phe20Ser | missense_variant | 1/16 | ENST00000367942.4 | |
LOC124904444 | XR_007066695.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATF6 | ENST00000367942.4 | c.59T>C | p.Phe20Ser | missense_variant | 1/16 | 1 | NM_007348.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0100 AC: 1526AN: 152158Hom.: 8 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0113 AC: 2843AN: 250562Hom.: 22 AF XY: 0.0122 AC XY: 1656AN XY: 135450
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GnomAD4 exome AF: 0.0162 AC: 23735AN: 1461030Hom.: 239 Cov.: 31 AF XY: 0.0163 AC XY: 11864AN XY: 726802
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GnomAD4 genome ? AF: 0.0100 AC: 1528AN: 152276Hom.: 8 Cov.: 32 AF XY: 0.00929 AC XY: 692AN XY: 74462
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ESP6500EA
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144
ExAC
?
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1478
Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at