rs2024092

Positions:

• chr19-1124032-G-A

Variant summary

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

The NM_014963.3(SBNO2):​c.442-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,607,266 control chromosomes in the GnomAD database, including 40,373 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 0.25 (5098 hom., cov: 32)
  • Exomes 𝑓: 0.22 (35275 hom.)
• Consequence: SBNO2 NM_014963.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001920
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBNO2	NM_014963.3	c.442-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000361757.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBNO2	ENST00000361757.8	c.442-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014963.3	P2
SBNO2	ENST00000592222.5	n.295-10C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
SBNO2	ENST00000438103.6	c.271-10C>T		splice_polypyrimidine_tract_variant, intron_variant		2		A2
SBNO2	ENST00000587024.5	c.442-10C>T		splice_polypyrimidine_tract_variant, intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38471 AN: 151964 Hom.: 5092 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.259

GnomAD3 exomes AF: 0.242 AC: 57574 AN: 238154 Hom.: 7423 AF XY: 0.235 AC XY: 30478 AN XY: 129784

Gnomad AFR exome AF: 0.304

Gnomad AMR exome AF: 0.372

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.131

Gnomad SAS exome AF: 0.226

Gnomad FIN exome AF: 0.248

Gnomad NFE exome AF: 0.219

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.215 AC: 313586 AN: 1455184 Hom.: 35275 Cov.: 34 AF XY: 0.215 AC XY: 155906 AN XY: 723490

Gnomad4 AFR exome AF: 0.309

Gnomad4 AMR exome AF: 0.365

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.253 AC: 38504 AN: 152082 Hom.: 5098 Cov.: 32 AF XY: 0.256 AC XY: 19033 AN XY: 74342

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.257

Alfa AF: 0.226 Hom.: 5901

Bravo AF: 0.260

Asia WGS AF: 0.193 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.0020
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: rs2024092; hg19: chr19-1124031; COSMIC: COSV62322039; COSMIC: COSV62322039;