rs3746162

Positions:

• chr19-1114120-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014963.3(SBNO2):​c.2077+111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,029,976 control chromosomes in the GnomAD database, including 23,295 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 0.18 (2815 hom., cov: 33)
  • Exomes 𝑓: 0.21 (20480 hom.)
• Consequence: SBNO2 NM_014963.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBNO2	NM_014963.3	c.2077+111G>A		intron_variant		ENST00000361757.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBNO2	ENST00000361757.8	c.2077+111G>A		intron_variant		1	NM_014963.3	P2
SBNO2	ENST00000438103.6	c.1906+111G>A		intron_variant		2		A2
SBNO2	ENST00000587024.5	c.2047+111G>A		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27491 AN: 152028 Hom.: 2812 Cov.: 33

Gnomad AFR AF: 0.0884

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.211 AC: 184975 AN: 877830 Hom.: 20480 AF XY: 0.209 AC XY: 90743 AN XY: 434106

Gnomad4 AFR exome AF: 0.0846

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.181 AC: 27511 AN: 152146 Hom.: 2815 Cov.: 33 AF XY: 0.183 AC XY: 13573 AN XY: 74372

Gnomad4 AFR AF: 0.0882

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.180

Alfa AF: 0.210 Hom.: 4318

Bravo AF: 0.171

Asia WGS AF: 0.176 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.62

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: rs3746162; hg19: chr19-1114119;