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GeneBe

12-123327582-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_001167856.3(SBNO1):c.1539-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,612,226 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 40 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 36 hom. )

Consequence

SBNO1
NM_001167856.3 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.08063
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.47
Variant links:
Genes affected
SBNO1 (HGNC:22973): (strawberry notch homolog 1) Predicted to enable chromatin DNA binding activity and histone binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-123327582-G-A is Benign according to our data. Variant chr12-123327582-G-A is described in ClinVar as [Benign]. Clinvar id is 721010.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1785/152076) while in subpopulation AFR AF= 0.0413 (1715/41496). AF 95% confidence interval is 0.0397. There are 40 homozygotes in gnomad4. There are 801 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1786 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SBNO1NM_001167856.3 linkuse as main transcriptc.1539-3C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000602398.3
SBNO1NM_018183.5 linkuse as main transcriptc.1536-3C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SBNO1ENST00000602398.3 linkuse as main transcriptc.1539-3C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 5 NM_001167856.3 P4A3KN83-1
SBNO1ENST00000420886.6 linkuse as main transcriptc.1539-3C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 P4A3KN83-1
SBNO1ENST00000267176.8 linkuse as main transcriptc.1536-3C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 5 A1A3KN83-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0118
AC:
1786
AN:
151958
Hom.:
40
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0415
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00322
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00623
GnomAD3 exomes
AF:
0.00303
AC:
757
AN:
249808
Hom.:
12
AF XY:
0.00212
AC XY:
286
AN XY:
135142
show subpopulations
Gnomad AFR exome
AF:
0.0411
Gnomad AMR exome
AF:
0.00213
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000797
Gnomad OTH exome
AF:
0.00165
GnomAD4 exome
AF:
0.00114
AC:
1664
AN:
1460150
Hom.:
36
Cov.:
30
AF XY:
0.000976
AC XY:
709
AN XY:
726492
show subpopulations
Gnomad4 AFR exome
AF:
0.0408
Gnomad4 AMR exome
AF:
0.00238
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000351
Gnomad4 OTH exome
AF:
0.00244
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0117
AC:
1785
AN:
152076
Hom.:
40
Cov.:
32
AF XY:
0.0108
AC XY:
801
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.0413
Gnomad4 AMR
AF:
0.00321
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00616
Alfa
AF:
0.00617
Hom.:
10
Bravo
AF:
0.0134
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.28
Cadd
Benign
17
Dann
Benign
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.081
dbscSNV1_RF
Benign
0.16
SpliceAI score (max)
0.11
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs75710010; hg19: chr12-123812129; API