chr22-41844793-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004599.4(SREBF2):​c.88+11435C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 151,912 control chromosomes in the GnomAD database, including 41,808 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 0.74 ( 41808 hom., cov: 30)

Consequence

SREBF2
NM_004599.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.303

Publications

6 publications found
Variant links:
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]
SREBF2 Gene-Disease associations (from GenCC):
  • multiple congenital anomalies/dysmorphic syndrome
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
  • hereditary spastic paraplegia
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SREBF2NM_004599.4 linkc.88+11435C>T intron_variant Intron 1 of 18 ENST00000361204.9 NP_004590.2 Q12772-1A0A024R1Q0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SREBF2ENST00000361204.9 linkc.88+11435C>T intron_variant Intron 1 of 18 1 NM_004599.4 ENSP00000354476.4 Q12772-1
SREBF2ENST00000424354.5 linkn.88+11435C>T intron_variant Intron 1 of 21 1 ENSP00000395728.1 G3V0I8
SREBF2ENST00000710853.1 linkc.-3+10766C>T intron_variant Intron 1 of 18 ENSP00000518526.1

Frequencies

GnomAD3 genomes
AF:
0.737
AC:
111937
AN:
151794
Hom.:
41743
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.815
Gnomad AMI
AF:
0.769
Gnomad AMR
AF:
0.811
Gnomad ASJ
AF:
0.705
Gnomad EAS
AF:
0.518
Gnomad SAS
AF:
0.763
Gnomad FIN
AF:
0.680
Gnomad MID
AF:
0.725
Gnomad NFE
AF:
0.699
Gnomad OTH
AF:
0.747
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.738
AC:
112065
AN:
151912
Hom.:
41808
Cov.:
30
AF XY:
0.738
AC XY:
54787
AN XY:
74246
show subpopulations
African (AFR)
AF:
0.815
AC:
33774
AN:
41426
American (AMR)
AF:
0.811
AC:
12384
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.705
AC:
2444
AN:
3468
East Asian (EAS)
AF:
0.518
AC:
2664
AN:
5142
South Asian (SAS)
AF:
0.763
AC:
3670
AN:
4810
European-Finnish (FIN)
AF:
0.680
AC:
7171
AN:
10544
Middle Eastern (MID)
AF:
0.721
AC:
212
AN:
294
European-Non Finnish (NFE)
AF:
0.699
AC:
47464
AN:
67936
Other (OTH)
AF:
0.750
AC:
1582
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1447
2894
4340
5787
7234
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
842
1684
2526
3368
4210
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.718
Hom.:
5124
Bravo
AF:
0.752
Asia WGS
AF:
0.704
AC:
2444
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
2.3
DANN
Benign
0.33
PhyloP100
-0.30
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs2284082; hg19: chr22-42240797; API