rs17848351
Positions:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_004599.4(SREBF2):āc.2704G>Cā(p.Val902Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00039 in 1,614,176 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 Likely benign (ā ).
Frequency
Genomes: š 0.00043 ( 1 hom., cov: 32)
Exomes š: 0.00039 ( 2 hom. )
Consequence
SREBF2
NM_004599.4 missense
NM_004599.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 7.25
Genes affected
SREBF2 (HGNC:11290): (sterol regulatory element binding transcription factor 2) This gene encodes a member of the a ubiquitously expressed transcription factor that controls cholesterol homeostasis by regulating transcription of sterol-regulated genes. The encoded protein contains a basic helix-loop-helix-leucine zipper (bHLH-Zip) domain and binds the sterol regulatory element 1 motif. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009077609).
BP6
?
Variant 22-41898747-G-C is Benign according to our data. Variant chr22-41898747-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3044042.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd4 at 66 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SREBF2 | NM_004599.4 | c.2704G>C | p.Val902Leu | missense_variant | 15/19 | ENST00000361204.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SREBF2 | ENST00000361204.9 | c.2704G>C | p.Val902Leu | missense_variant | 15/19 | 1 | NM_004599.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000427 AC: 65AN: 152204Hom.: 1 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000633 AC: 159AN: 251304Hom.: 0 AF XY: 0.000604 AC XY: 82AN XY: 135836
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GnomAD4 exome AF: 0.000386 AC: 564AN: 1461854Hom.: 2 Cov.: 31 AF XY: 0.000395 AC XY: 287AN XY: 727218
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GnomAD4 genome ? AF: 0.000433 AC: 66AN: 152322Hom.: 1 Cov.: 32 AF XY: 0.000456 AC XY: 34AN XY: 74486
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
SREBF2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 20, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of methylation at K907 (P = 0.0793);
MVP
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