chr22-41868792-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_004599.4(SREBF2):c.720G>A(p.Pro240=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000873 in 1,607,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00091 ( 0 hom. )
Consequence
SREBF2
NM_004599.4 splice_region, synonymous
NM_004599.4 splice_region, synonymous
Scores
2
Splicing: ADA: 0.9931
1
1
Clinical Significance
Conservation
PhyloP100: 0.847
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 Likely_benign. Variant got -6 ACMG points.
BP6
?
Variant 22-41868792-G-A is Benign according to our data. Variant chr22-41868792-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3037307.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 82 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SREBF2 | NM_004599.4 | c.720G>A | p.Pro240= | splice_region_variant, synonymous_variant | 3/19 | ENST00000361204.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SREBF2 | ENST00000361204.9 | c.720G>A | p.Pro240= | splice_region_variant, synonymous_variant | 3/19 | 1 | NM_004599.4 | P3 | |
SREBF2 | ENST00000424354.5 | c.720G>A | p.Pro240= | splice_region_variant, synonymous_variant, NMD_transcript_variant | 3/22 | 1 | |||
SREBF2 | ENST00000710853.1 | c.630G>A | p.Pro210= | splice_region_variant, synonymous_variant | 3/19 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000539 AC: 82AN: 152192Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000460 AC: 108AN: 234610Hom.: 0 AF XY: 0.000386 AC XY: 49AN XY: 127030
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GnomAD4 exome AF: 0.000908 AC: 1321AN: 1454732Hom.: 0 Cov.: 32 AF XY: 0.000871 AC XY: 630AN XY: 723150
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GnomAD4 genome ? AF: 0.000538 AC: 82AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35AN XY: 74466
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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 | May 07, 2019 | 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
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Prediction
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Benign
Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -15
Find out detailed SpliceAI scores and Pangolin per-transcript scores at