19-1108470-G-A

Position:

• chr19-1108470-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014963.3(SBNO2):​c.3851C>T​(p.Ala1284Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,076,608 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: SBNO2 NM_014963.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82

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]

ACMG classification

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=0.05733314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBNO2	NM_014963.3	c.3851C>T	p.Ala1284Val	missense_variant	32/32	ENST00000361757.8	NP_055778.2
SBNO2	NM_001100122.2	c.3680C>T	p.Ala1227Val	missense_variant	29/29		NP_001093592.1
SBNO2	XM_047438466.1	c.2654C>T	p.Ala885Val	missense_variant	29/29		XP_047294422.1
SBNO2	XM_011527804.4	c.*181C>T		3_prime_UTR_variant	32/32		XP_011526106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBNO2	ENST00000361757.8	c.3851C>T	p.Ala1284Val	missense_variant	32/32	1	NM_014963.3	ENSP00000354733.2
SBNO2	ENST00000587024.5	c.3821C>T	p.Ala1274Val	missense_variant	32/32	2		ENSP00000468520.1
SBNO2	ENST00000438103.6	c.3680C>T	p.Ala1227Val	missense_variant	29/29	2		ENSP00000400762.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000186 AC: 2 AN: 1076608 Hom.: 0 Cov.: 33 AF XY: 0.00000388 AC XY: 2 AN XY: 516010

Gnomad4 AFR exome AF: 0.0000491

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000242

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 27, 2023

The c.3851C>T (p.A1284V) alteration is located in exon 32 (coding exon 31) of the SBNO2 gene. This alteration results from a C to T substitution at nucleotide position 3851, causing the alanine (A) at amino acid position 1284 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	0.081
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T;.;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.17	N;N;.
REVEL	Benign	0.054
Sift	Benign	0.58	T;T;.
Sift4G	Benign	0.15	T;T;T
Polyphen		0.32	B;B;.
Vest4		0.097
MutPred		0.18		Loss of disorder (P = 0.0977);.;.;
MVP		0.13
MPC		0.41
ClinPred		0.15	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.039
gMVP		0.25

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

Other links and lift over

dbSNP: rs2079702115; hg19: chr19-1108469;