12-123321736-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001167856.3(SBNO1):c.2126-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,458 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (11 hom.)
• Consequence: SBNO1 NM_001167856.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003928
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.309

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 12-123321736-C-T is Benign according to our data. Variant chr12-123321736-C-T is described in ClinVar as [Benign]. Clinvar id is 723596.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00647 (985/152250) while in subpopulation AFR AF= 0.0222 (921/41534). AF 95% confidence interval is 0.021. There are 9 homozygotes in gnomad4. There are 475 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 988 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBNO1	NM_001167856.3	c.2126-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000602398.3
SBNO1	NM_018183.5	c.2123-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBNO1	ENST00000602398.3	c.2126-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001167856.3	P4
SBNO1	ENST00000420886.6	c.2126-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		P4
SBNO1	ENST00000267176.8	c.2123-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 988 AN: 152132 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00315

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00157 AC: 395 AN: 250988 Hom.: 6 AF XY: 0.00105 AC XY: 142 AN XY: 135634

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.000870

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.000663 AC: 969 AN: 1461208 Hom.: 11 Cov.: 31 AF XY: 0.000590 AC XY: 429 AN XY: 726956

Gnomad4 AFR exome AF: 0.0234

Gnomad4 AMR exome AF: 0.00119

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.00142

GnomAD4 genome AF: 0.00647 AC: 985 AN: 152250 Hom.: 9 Cov.: 32 AF XY: 0.00638 AC XY: 475 AN XY: 74444

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00340 Hom.: 2

Bravo AF: 0.00762

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	4.4
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00039
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs146861005; hg19: chr12-123806283;