Variant 19-1108501-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014963.3(SBNO2):c.3820T>G(p.Phe1274Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000289 in 1,211,548 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 1 hom. )

Consequence

SBNO2
NM_014963.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16

Variant links:

Genes affected

SBNO2 (HGNC:29158): (strawberry notch homolog 2) Predicted to enable chromatin DNA binding activity and histone binding activity. Involved in several processes, including cellular response to interleukin-6; macrophage activation involved in immune response; and negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SBNO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12322137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBNO2	NM_014963.3 linkuse as main transcript	c.3820T>G	p.Phe1274Val	missense_variant	32/32	ENST00000361757.8	NP_055778.2	Q9Y2G9-1
SBNO2	NM_001100122.2 linkuse as main transcript	c.3649T>G	p.Phe1217Val	missense_variant	29/29		NP_001093592.1	Q9Y2G9-3
SBNO2	XM_047438466.1 linkuse as main transcript	c.2623T>G	p.Phe875Val	missense_variant	29/29		XP_047294422.1
SBNO2	XM_011527804.4 linkuse as main transcript	c.*150T>G		3_prime_UTR_variant	32/32		XP_011526106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SBNO2	ENST00000361757.8 linkuse as main transcript	c.3820T>G	p.Phe1274Val	missense_variant	32/32	1	NM_014963.3	ENSP00000354733.2	Q9Y2G9-1
SBNO2	ENST00000587024.5 linkuse as main transcript	c.3790T>G	p.Phe1264Val	missense_variant	32/32	2		ENSP00000468520.1	K7ES28
SBNO2	ENST00000438103.6 linkuse as main transcript	c.3649T>G	p.Phe1217Val	missense_variant	29/29	2		ENSP00000400762.1	Q9Y2G9-3

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

148584

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000310

AC:

AN:

1062964

Hom.:

Cov.:

AF XY:

0.0000394

AC XY:

AN XY:

507356

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000510

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000276

Gnomad4 OTH exome

AF:

0.0000982

GnomAD4 genome

AF:

0.0000135

AC:

AN:

148584

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72426

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2023

The c.3820T>G (p.F1274V) alteration is located in exon 32 (coding exon 31) of the SBNO2 gene. This alteration results from a T to G substitution at nucleotide position 3820, causing the phenylalanine (F) at amino acid position 1274 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.014

T;.;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.10

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

L;.;.

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.86

N;N;.

REVEL

Benign

0.063

Sift

Benign

0.18

T;T;.

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

0.76

P;D;.

Vest4

0.22

MutPred

0.32

Gain of phosphorylation at S1275 (P = 0.1576);.;.;

MVP

0.29

MPC

0.57

ClinPred

0.30

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.23

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over