12-123320714-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_001167856.3(SBNO1):c.2476C>T(p.Pro826Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,608,602 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0090 (13 hom., cov: 32)
  • Exomes 𝑓: 0.013 (138 hom.)
• Consequence: SBNO1 NM_001167856.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.06

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PP2: Missense variant where missense usually causes diseases, SBNO1
• BP4: Computational evidence support a benign effect (MetaRNN=0.00358662).
• BP6: Variant 12-123320714-G-A is Benign according to our data. Variant chr12-123320714-G-A is described in ClinVar as [Benign]. Clinvar id is 782334.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 1366 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBNO1	NM_001167856.3	c.2476C>T	p.Pro826Ser	missense_variant	18/32	ENST00000602398.3
SBNO1	NM_018183.5	c.2473C>T	p.Pro825Ser	missense_variant	18/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBNO1	ENST00000602398.3	c.2476C>T	p.Pro826Ser	missense_variant	18/32	5	NM_001167856.3	P4
SBNO1	ENST00000420886.6	c.2476C>T	p.Pro826Ser	missense_variant	17/31	1		P4
SBNO1	ENST00000267176.8	c.2473C>T	p.Pro825Ser	missense_variant	18/32	5		A1

Frequencies

GnomAD3 genomes AF: 0.00898 AC: 1366 AN: 152184 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00265

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0149

Gnomad OTH AF: 0.00573

GnomAD3 exomes AF: 0.00911 AC: 2241 AN: 245886 Hom.: 13 AF XY: 0.00950 AC XY: 1263 AN XY: 132932

Gnomad AFR exome AF: 0.00198

Gnomad AMR exome AF: 0.00459

Gnomad ASJ exome AF: 0.00468

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00629

Gnomad FIN exome AF: 0.00877

Gnomad NFE exome AF: 0.0142

Gnomad OTH exome AF: 0.00752

GnomAD4 exome AF: 0.0129 AC: 18757 AN: 1456300 Hom.: 138 Cov.: 31 AF XY: 0.0127 AC XY: 9193 AN XY: 724390

Gnomad4 AFR exome AF: 0.00197

Gnomad4 AMR exome AF: 0.00470

Gnomad4 ASJ exome AF: 0.00440

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00664

Gnomad4 FIN exome AF: 0.00946

Gnomad4 NFE exome AF: 0.0149

Gnomad4 OTH exome AF: 0.0119

GnomAD4 genome AF: 0.00898 AC: 1367 AN: 152302 Hom.: 13 Cov.: 32 AF XY: 0.00832 AC XY: 620 AN XY: 74476

Gnomad4 AFR AF: 0.00265

Gnomad4 AMR AF: 0.00419

Gnomad4 ASJ AF: 0.00663

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00663

Gnomad4 FIN AF: 0.0102

Gnomad4 NFE AF: 0.0149

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.0119 Hom.: 7

Bravo AF: 0.00825

TwinsUK AF: 0.0159 AC: 59

ALSPAC AF: 0.0119 AC: 46

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.0121 AC: 104

ExAC AF: 0.00905 AC: 1099

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0118

EpiControl AF: 0.0126

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	16
Dann	Benign	0.37
DEOGEN2	Benign	0.0097	T;.;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	T;T;.
MetaRNN	Benign	0.0036	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N;.;N
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.20	N;N;.
REVEL	Benign	0.085
Sift	Benign	0.59	T;T;.
Sift4G	Benign	0.76	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.14
MVP		0.068
MPC		0.68
ClinPred		0.0023	T
GERP RS		2.9
Varity_R		0.021
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs61760909; hg19: chr12-123805261;