rs2297508
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_004176.5(SREBF1):c.*619G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 437,516 control chromosomes in the GnomAD database, including 68,804 homozygotes. 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 0.57 ( 25617 hom., cov: 33)
Exomes 𝑓: 0.53 ( 43187 hom. )
Consequence
SREBF1
NM_004176.5 3_prime_UTR
NM_004176.5 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.0240
Genes affected
SREBF1 (HGNC:11289): (sterol regulatory element binding transcription factor 1) This gene encodes a basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor that binds to the sterol regulatory element-1 (SRE1), which is a motif that is found in the promoter of the low density lipoprotein receptor gene and other genes involved in sterol biosynthesis. The encoded protein is synthesized as a precursor that is initially attached to the nuclear membrane and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription. This cleaveage is inhibited by sterols. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternative promoter usage and splicing result in multiple transcript variants, including SREBP-1a and SREBP-1c, which correspond to RefSeq transcript variants 2 and 3, respectively. [provided by RefSeq, Nov 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SREBF1 | NM_004176.5 | c.*619G>C | 3_prime_UTR_variant | 19/19 | ENST00000261646.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SREBF1 | ENST00000261646.11 | c.*619G>C | 3_prime_UTR_variant | 19/19 | 1 | NM_004176.5 | P4 | ||
SREBF1 | ENST00000395757.6 | c.3156G>C | p.Gly1052= | synonymous_variant | 18/19 | 2 | |||
SREBF1 | ENST00000485080.6 | c.*34G>C | 3_prime_UTR_variant, NMD_transcript_variant | 3/5 | 5 | ||||
SREBF1 | ENST00000578469.1 | c.*34G>C | 3_prime_UTR_variant, NMD_transcript_variant | 2/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.571 AC: 86684AN: 151876Hom.: 25589 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
86684
AN:
151876
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.498 AC: 59899AN: 120346Hom.: 16492 AF XY: 0.493 AC XY: 32640AN XY: 66186
GnomAD3 exomes
AF:
AC:
59899
AN:
120346
Hom.:
AF XY:
AC XY:
32640
AN XY:
66186
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.529 AC: 150938AN: 285520Hom.: 43187 Cov.: 0 AF XY: 0.509 AC XY: 83622AN XY: 164168
GnomAD4 exome
AF:
AC:
150938
AN:
285520
Hom.:
Cov.:
0
AF XY:
AC XY:
83622
AN XY:
164168
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.571 AC: 86772AN: 151996Hom.: 25617 Cov.: 33 AF XY: 0.559 AC XY: 41497AN XY: 74274
GnomAD4 genome
?
AF:
AC:
86772
AN:
151996
Hom.:
Cov.:
33
AF XY:
AC XY:
41497
AN XY:
74274
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1059
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at