chr19-1124836-A-G

Variant names:

• chr19-1124836-A-G
• rs740495
• NM_014963.3:c.442-814T>C

Variant summary

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

The NM_014963.3(SBNO2):​c.442-814T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,836 control chromosomes in the GnomAD database, including 12,393 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 0.38 (12393 hom., cov: 30)
• Consequence: SBNO2 NM_014963.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.77
• Publications: 38 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBNO2	NM_014963.3	c.442-814T>C		intron_variant	Intron 5 of 31	ENST00000361757.8	NP_055778.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBNO2	ENST00000361757.8	c.442-814T>C		intron_variant	Intron 5 of 31	1	NM_014963.3	ENSP00000354733.2
SBNO2	ENST00000592222.5	n.295-814T>C		intron_variant	Intron 2 of 13	1
SBNO2	ENST00000587024.5	c.442-814T>C		intron_variant	Intron 5 of 31	2		ENSP00000468520.1
SBNO2	ENST00000438103.6	c.271-814T>C		intron_variant	Intron 2 of 28	2		ENSP00000400762.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57750 AN: 151720 Hom.: 12366 Cov.: 30

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.353

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.381 AC: 57828 AN: 151836 Hom.: 12393 Cov.: 30 AF XY: 0.383 AC XY: 28397 AN XY: 74188

African (AFR) AF: 0.597 AC: 24708 AN: 41384

American (AMR) AF: 0.381 AC: 5812 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1070 AN: 3462

East Asian (EAS) AF: 0.352 AC: 1813 AN: 5150

South Asian (SAS) AF: 0.340 AC: 1630 AN: 4790

European-Finnish (FIN) AF: 0.314 AC: 3315 AN: 10568

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18397 AN: 67916

Other (OTH) AF: 0.353 AC: 743 AN: 2104

Alfa AF: 0.305 Hom.: 28405

Bravo AF: 0.392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.72
DANN	Benign	0.31
PhyloP100		-3.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs740495; hg19: chr19-1124835;