Variant 12-123321736-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Variant links:

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]

SBNO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 985 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBNO1	NM_001167856.3 linkuse as main transcript	c.2126-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5 linkuse as main transcript	c.2123-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_060653.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
SBNO1	ENST00000602398.3 linkuse as main transcript	c.2126-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5	NM_001167856.3	ENSP00000473665	P4	A3KN83-1
SBNO1	ENST00000420886.6 linkuse as main transcript	c.2126-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000387361	P4	A3KN83-1
SBNO1	ENST00000267176.8 linkuse as main transcript	c.2123-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000267176	A1	A3KN83-2

Frequencies

GnomAD3 genomes

AF:

0.00649

AC:

988

AN:

152132

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00105

AC XY:

142

AN XY:

135634

show subpopulations

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.:

Cov.:

AF XY:

0.000590

AC XY:

429

AN XY:

726956

show subpopulations

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.:

Cov.:

AF XY:

0.00638

AC XY:

475

AN XY:

74444

show subpopulations

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.:

Bravo

AF:

0.00762

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over