17-17814669-G-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_004176.5(SREBF1):c.2681C>T(p.Ala894Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000782 in 1,572,864 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00014 ( 2 hom., cov: 33)
Exomes 𝑓: 0.000072 ( 0 hom. )
Consequence
SREBF1
NM_004176.5 missense
NM_004176.5 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 5.71
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008975148).
BP6
?
Variant 17-17814669-G-A is Benign according to our data. Variant chr17-17814669-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 740150.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SREBF1 | NM_004176.5 | c.2681C>T | p.Ala894Val | missense_variant | 15/19 | ENST00000261646.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SREBF1 | ENST00000261646.11 | c.2681C>T | p.Ala894Val | missense_variant | 15/19 | 1 | NM_004176.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152226Hom.: 2 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
21
AN:
152226
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: 0.000315 AC: 59AN: 187340Hom.: 0 AF XY: 0.000215 AC XY: 22AN XY: 102502
GnomAD3 exomes
AF:
AC:
59
AN:
187340
Hom.:
AF XY:
AC XY:
22
AN XY:
102502
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: 0.0000718 AC: 102AN: 1420520Hom.: 0 Cov.: 32 AF XY: 0.0000611 AC XY: 43AN XY: 704220
GnomAD4 exome
AF:
AC:
102
AN:
1420520
Hom.:
Cov.:
32
AF XY:
AC XY:
43
AN XY:
704220
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: 0.000138 AC: 21AN: 152344Hom.: 2 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74492
GnomAD4 genome
?
AF:
AC:
21
AN:
152344
Hom.:
Cov.:
33
AF XY:
AC XY:
10
AN XY:
74492
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:
ExAC
?
AF:
AC:
20
Asia WGS
AF:
AC:
5
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
1.0
.;D;D
Vest4
MutPred
0.45
.;.;Loss of disorder (P = 0.0809);
MVP
MPC
0.90
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at