NM_014963.3:c.442-10C>T

Variant names:

• chr19-1124032-G-A
• rs2024092
• NM_014963.3:c.442-10C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014963.3(SBNO2):​c.442-10C>T variant causes a 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 intron
• Scores: Splicing: ADA: 0.00001920
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 64 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014963.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBNO2	NM_014963.3	MANE Select	c.442-10C>T		intron	N/A	NP_055778.2
	SBNO2	NM_001100122.2		c.271-10C>T		intron	N/A	NP_001093592.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBNO2	ENST00000361757.8	TSL:1 MANE Select	c.442-10C>T		intron	N/A	ENSP00000354733.2
	SBNO2	ENST00000592222.5	TSL:1	n.295-10C>T		intron	N/A
	SBNO2	ENST00000954690.1		c.442-10C>T		intron	N/A	ENSP00000624749.1

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

GnomAD2 exomes AF: 0.242 AC: 57574 AN: 238154 AF XY: 0.235

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 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

African (AFR) AF: 0.309 AC: 10287 AN: 33336

American (AMR) AF: 0.365 AC: 16046 AN: 43910

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 5159 AN: 25932

East Asian (EAS) AF: 0.162 AC: 6410 AN: 39594

South Asian (SAS) AF: 0.225 AC: 19159 AN: 85296

European-Finnish (FIN) AF: 0.241 AC: 12576 AN: 52108

Middle Eastern (MID) AF: 0.235 AC: 1328 AN: 5652

European-Non Finnish (NFE) AF: 0.208 AC: 230194 AN: 1109216

Other (OTH) AF: 0.207 AC: 12427 AN: 60140

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

African (AFR) AF: 0.311 AC: 12905 AN: 41478

American (AMR) AF: 0.333 AC: 5091 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3468

East Asian (EAS) AF: 0.129 AC: 668 AN: 5182

South Asian (SAS) AF: 0.220 AC: 1063 AN: 4822

European-Finnish (FIN) AF: 0.259 AC: 2743 AN: 10582

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.214 AC: 14559 AN: 67944

Other (OTH) AF: 0.257 AC: 542 AN: 2112

Alfa AF: 0.230 Hom.: 12877

Bravo AF: 0.260

Asia WGS AF: 0.193 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.60
PhyloP100		-0.0090
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2024092; hg19: chr19-1124031; COSMIC: COSV62322039; COSMIC: COSV62322039;