rs193920847

Variant names:

• chr12-123350306-T-C
• rs193920847
• NM_001167856.3:c.132+4A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-123350306-T-C
• chr12-123350306-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001167856.3(SBNO1):​c.132+4A>G variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000000684 in 1,461,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SBNO1 NM_001167856.3 splice_region, intron
• Scores: Splicing: ADA: 0.9902
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.51
• Publications: 0 publications found

Genes affected

SBNO1 (HGNC:22973): (strawberry notch homolog 1) Predicted to enable chromatin DNA binding activity and histone binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBNO1	NM_001167856.3	c.132+4A>G		splice_region_variant, intron_variant	Intron 2 of 31	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5	c.132+4A>G		splice_region_variant, intron_variant	Intron 2 of 31		NP_060653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBNO1	ENST00000602398.3	c.132+4A>G		splice_region_variant, intron_variant	Intron 2 of 31	5	NM_001167856.3	ENSP00000473665.1
SBNO1	ENST00000420886.6	c.132+4A>G		splice_region_variant, intron_variant	Intron 1 of 30	1		ENSP00000387361.2
SBNO1	ENST00000267176.8	c.132+4A>G		splice_region_variant, intron_variant	Intron 2 of 31	5		ENSP00000267176.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461260 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727004

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111816

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Benign	0.97
PhyloP100		6.5
PromoterAI		-0.0031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.78
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: rs193920847; hg19: chr12-123834853;