12-123321537-T-C

Position:

• chr12-123321537-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001167856.3(SBNO1):​c.2321A>G​(p.Asn774Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00341 in 1,608,034 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (16 hom.)
• Consequence: SBNO1 NM_001167856.3 missense, splice_region
• Scores: Splicing: ADA: 0.0009088
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.56

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041263103).
• BP6: Variant 12-123321537-T-C is Benign according to our data. Variant chr12-123321537-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 709935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 370 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBNO1	NM_001167856.3	c.2321A>G	p.Asn774Ser	missense_variant, splice_region_variant	17/32	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5	c.2318A>G	p.Asn773Ser	missense_variant, splice_region_variant	17/32		NP_060653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBNO1	ENST00000602398.3	c.2321A>G	p.Asn774Ser	missense_variant, splice_region_variant	17/32	5	NM_001167856.3	ENSP00000473665	P4
SBNO1	ENST00000420886.6	c.2321A>G	p.Asn774Ser	missense_variant, splice_region_variant	16/31	1		ENSP00000387361	P4
SBNO1	ENST00000267176.8	c.2318A>G	p.Asn773Ser	missense_variant, splice_region_variant	17/32	5		ENSP00000267176	A1

Frequencies

GnomAD3 genomes AF: 0.00243 AC: 370 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00482

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00253 AC: 635 AN: 250928 Hom.: 4 AF XY: 0.00242 AC XY: 328 AN XY: 135618

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000786

Gnomad NFE exome AF: 0.00522

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00352 AC: 5117 AN: 1455732 Hom.: 16 Cov.: 28 AF XY: 0.00339 AC XY: 2454 AN XY: 724672

Gnomad4 AFR exome AF: 0.000300

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00107

Gnomad4 NFE exome AF: 0.00446

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.00243 AC: 370 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.00218 AC XY: 162 AN XY: 74474

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00482

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.00372 Hom.: 3

Bravo AF: 0.00233

TwinsUK AF: 0.00405 AC: 15

ALSPAC AF: 0.00701 AC: 27

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00442 AC: 38

ExAC AF: 0.00268 AC: 326

EpiCase AF: 0.00273

EpiControl AF: 0.00385

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.0065	T;.;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.0025
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D;D;.
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.0041	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.020	N;N;.
REVEL	Benign	0.059
Sift	Benign	0.35	T;T;.
Sift4G	Benign	0.73	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.079
MVP		0.068
MPC		0.54
ClinPred		0.031	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.067
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00091
dbscSNV1_RF	Benign	0.050
SpliceAI score (max)		0.010		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: rs114314586; hg19: chr12-123806084;