Variant chr19-1108618-C-T 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.3703G>A(p.Ala1235Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000216 in 1,437,464 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

SBNO2
NM_014963.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.974

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=0.040439814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SBNO2	NM_014963.3 linkuse as main transcript	c.3703G>A	p.Ala1235Thr	missense_variant	32/32	ENST00000361757.8
SBNO2	NM_001100122.2 linkuse as main transcript	c.3532G>A	p.Ala1178Thr	missense_variant	29/29
SBNO2	XM_047438466.1 linkuse as main transcript	c.2506G>A	p.Ala836Thr	missense_variant	29/29
SBNO2	XM_011527804.4 linkuse as main transcript	c.*33G>A		3_prime_UTR_variant	32/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBNO2	ENST00000361757.8 linkuse as main transcript	c.3703G>A	p.Ala1235Thr	missense_variant	32/32	1	NM_014963.3	P2	Q9Y2G9-1
SBNO2	ENST00000587024.5 linkuse as main transcript	c.3673G>A	p.Ala1225Thr	missense_variant	32/32	2		A2
SBNO2	ENST00000438103.6 linkuse as main transcript	c.3532G>A	p.Ala1178Thr	missense_variant	29/29	2		A2	Q9Y2G9-3
SBNO2	ENST00000587673.5 linkuse as main transcript	n.1156G>A		non_coding_transcript_exon_variant	7/7	5

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150912

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000969

AC:

AN:

51592

Hom.:

AF XY:

0.0000338

AC XY:

AN XY:

29612

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000340

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:

0.0000557

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000225

AC:

AN:

1286552

Hom.:

Cov.:

AF XY:

0.0000174

AC XY:

AN XY:

632624

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000212

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73670

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000194

Hom.:

Bravo

AF:

0.0000264

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

Apr 18, 2023

The c.3703G>A (p.A1235T) alteration is located in exon 32 (coding exon 31) of the SBNO2 gene. This alteration results from a G to A substitution at nucleotide position 3703, causing the alanine (A) at amino acid position 1235 to be replaced by a threonine (T). 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

0.072

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.1

DANN

Benign

0.97

DEOGEN2

Benign

0.013

T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.055

M_CAP

Benign

0.015

MetaRNN

Benign

0.040

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.34

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.18

N;N;.

REVEL

Benign

0.0010

Sift

Benign

0.59

T;T;.

Sift4G

Benign

0.46

T;T;T

Polyphen

0.0020

B;B;.

Vest4

0.023

MutPred

0.21

Gain of glycosylation at A1235 (P = 0.0189);.;.;

MVP

0.076

MPC

0.39

ClinPred

0.025

GERP RS

-4.7

Varity_R

0.060

gMVP

0.15

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

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