dbSNP rs1060105: SBNO1:p.Ser729Asn (chr12-123321672-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001167856.3(SBNO1):c.2186G>A(p.Ser729Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,613,612 control chromosomes in the GnomAD database, including 32,584 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 0.16 ( 2372 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30212 hom. )

Consequence

SBNO1
NM_001167856.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.22

Publications

80 publications found

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]

SBNO1 links:

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 (MetaRNN=0.0014118552).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBNO1	NM_001167856.3 link	c.2186G>A	p.Ser729Asn	missense_variant	Exon 17 of 32	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5 link	c.2183G>A	p.Ser728Asn	missense_variant	Exon 17 of 32		NP_060653.3	A3KN83-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SBNO1	ENST00000602398.3 link	c.2186G>A	p.Ser729Asn	missense_variant	Exon 17 of 32	5	NM_001167856.3	ENSP00000473665.1	A3KN83-1
SBNO1	ENST00000420886.6 link	c.2186G>A	p.Ser729Asn	missense_variant	Exon 16 of 31	1		ENSP00000387361.2	A3KN83-1
SBNO1	ENST00000267176.8 link	c.2183G>A	p.Ser728Asn	missense_variant	Exon 17 of 32	5		ENSP00000267176.4	A3KN83-2

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24718

AN:

152002

Hom.:

2364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0793

Gnomad AMI

AF:

0.172

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.00423

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.171

GnomAD2 exomes

AF:

0.191

AC:

47988

AN:

251348

AF XY:

0.195

show subpopulations

Gnomad AFR exome

AF:

0.0763

Gnomad AMR exome

AF:

0.231

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.198

AC:

289508

AN:

1461492

Hom.:

30212

Cov.:

AF XY:

0.200

AC XY:

145502

AN XY:

727064

show subpopulations

African (AFR)

AF:

0.0720

AC:

2409

AN:

33478

American (AMR)

AF:

0.225

AC:

10060

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

6219

AN:

26124

East Asian (EAS)

AF:

0.000554

AC:

AN:

39690

South Asian (SAS)

AF:

0.226

AC:

19484

AN:

86248

European-Finnish (FIN)

AF:

0.218

AC:

11651

AN:

53418

Middle Eastern (MID)

AF:

0.225

AC:

1299

AN:

5768

European-Non Finnish (NFE)

AF:

0.204

AC:

227219

AN:

1111666

Other (OTH)

AF:

0.185

AC:

11145

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

11640

23280

34919

46559

58199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7784

15568

23352

31136

38920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.163

AC:

24726

AN:

152120

Hom.:

2372

Cov.:

AF XY:

0.164

AC XY:

12219

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0790

AC:

3280

AN:

41532

American (AMR)

AF:

0.182

AC:

2780

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

869

AN:

3472

East Asian (EAS)

AF:

0.00424

AC:

AN:

5186

South Asian (SAS)

AF:

0.216

AC:

1041

AN:

4816

European-Finnish (FIN)

AF:

0.223

AC:

2359

AN:

10562

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.203

AC:

13783

AN:

67978

Other (OTH)

AF:

0.169

AC:

357

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1009

2018

3026

4035

5044

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.190

Hom.:

11068

Bravo

AF:

0.155

TwinsUK

AF:

0.200

AC:

742

ALSPAC

AF:

0.197

AC:

760

ESP6500AA

AF:

0.0824

AC:

363

ESP6500EA

AF:

0.197

AC:

1698

ExAC

AF:

0.187

AC:

22705

Asia WGS

AF:

0.101

AC:

352

AN:

3478

EpiCase

AF:

0.216

EpiControl

AF:

0.209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;.;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;.

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.;M

PhyloP100

7.2

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.43

N;N;.

REVEL

Benign

0.11

Sift

Benign

0.14

T;T;.

Sift4G

Benign

0.65

T;T;T

Polyphen

0.085

B;B;B

Vest4

0.21

MPC

0.67

ClinPred

0.038

GERP RS

5.5

Varity_R

0.32

gMVP

0.35

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over