Variant 19-1108264-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014963.3(SBNO2):c.4057A>T(p.Ile1353Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000686 in 1,522,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00073 ( 0 hom. )

Consequence

SBNO2
NM_014963.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06602043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBNO2	NM_014963.3 linkuse as main transcript	c.4057A>T	p.Ile1353Phe	missense_variant	32/32	ENST00000361757.8	NP_055778.2	Q9Y2G9-1
SBNO2	NM_001100122.2 linkuse as main transcript	c.3886A>T	p.Ile1296Phe	missense_variant	29/29		NP_001093592.1	Q9Y2G9-3
SBNO2	XM_047438466.1 linkuse as main transcript	c.2860A>T	p.Ile954Phe	missense_variant	29/29		XP_047294422.1
SBNO2	XM_011527804.4 linkuse as main transcript	c.*387A>T		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.4057A>T	p.Ile1353Phe	missense_variant	32/32	1	NM_014963.3	ENSP00000354733.2	Q9Y2G9-1
SBNO2	ENST00000587024.5 linkuse as main transcript	c.4027A>T	p.Ile1343Phe	missense_variant	32/32	2		ENSP00000468520.1	K7ES28
SBNO2	ENST00000438103.6 linkuse as main transcript	c.3886A>T	p.Ile1296Phe	missense_variant	29/29	2		ENSP00000400762.1	Q9Y2G9-3

Frequencies

GnomAD3 genomes

AF:

0.000304

AC:

AN:

151508

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000620

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000160

AC:

AN:

124764

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

68400

show subpopulations

Gnomad AFR exome

AF:

0.000292

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000404

Gnomad OTH exome

AF:

0.000553

GnomAD4 exome

AF:

0.000729

AC:

999

AN:

1371058

Hom.:

Cov.:

AF XY:

0.000690

AC XY:

467

AN XY:

676710

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000634

Gnomad4 NFE exome

AF:

0.000891

Gnomad4 OTH exome

AF:

0.000711

GnomAD4 genome

AF:

0.000304

AC:

AN:

151508

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

74024

show subpopulations

Gnomad4 AFR

AF:

0.0000969

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000620

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000407

Hom.:

Bravo

AF:

0.000272

ExAC

AF:

0.000242

AC:

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

Feb 17, 2023

The c.4057A>T (p.I1353F) alteration is located in exon 32 (coding exon 31) of the SBNO2 gene. This alteration results from a A to T substitution at nucleotide position 4057, causing the isoleucine (I) at amino acid position 1353 to be replaced by a phenylalanine (F). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

T;.;T

Eigen

Benign

0.15

Eigen_PC

Benign

0.071

FATHMM_MKL

Uncertain

0.76

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.066

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

2.0

M;.;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.60

N;N;.

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.99

D;D;.

Vest4

0.33

MVP

0.61

MPC

1.6

ClinPred

0.095

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.51

gMVP

0.48

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