chr12-123309316-T-C

Variant names:

• chr12-123309316-T-C
• rs61760955
• NM_001167856.3:c.3624A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001167856.3(SBNO1):​c.3624A>G​(p.Ser1208Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,613,318 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (57 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (49 hom.)
• Consequence: SBNO1 NM_001167856.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.71
• Publications: 2 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 12-123309316-T-C is Benign according to our data. Variant chr12-123309316-T-C is described in ClinVar as [Benign]. Clinvar id is 775320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.71 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0144 (2187/152306) while in subpopulation AFR AF = 0.0486 (2020/41564). AF 95% confidence interval is 0.0468. There are 57 homozygotes in GnomAd4. There are 1021 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2187 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBNO1	NM_001167856.3	c.3624A>G	p.Ser1208Ser	synonymous_variant	Exon 28 of 32	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5	c.3621A>G	p.Ser1207Ser	synonymous_variant	Exon 28 of 32		NP_060653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBNO1	ENST00000602398.3	c.3624A>G	p.Ser1208Ser	synonymous_variant	Exon 28 of 32	5	NM_001167856.3	ENSP00000473665.1
SBNO1	ENST00000420886.6	c.3624A>G	p.Ser1208Ser	synonymous_variant	Exon 27 of 31	1		ENSP00000387361.2
SBNO1	ENST00000267176.8	c.3621A>G	p.Ser1207Ser	synonymous_variant	Exon 28 of 32	5		ENSP00000267176.4

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2180 AN: 152188 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.0485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00374 AC: 940 AN: 251282 AF XY: 0.00281

Gnomad AFR exome AF: 0.0476

Gnomad AMR exome AF: 0.00197

Gnomad ASJ exome AF: 0.00516

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000282

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00162 AC: 2373 AN: 1461012 Hom.: 49 Cov.: 30 AF XY: 0.00145 AC XY: 1053 AN XY: 726924

African (AFR) AF: 0.0490 AC: 1639 AN: 33456

American (AMR) AF: 0.00212 AC: 95 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00639 AC: 167 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00433 AC: 25 AN: 5768

European-Non Finnish (NFE) AF: 0.000191 AC: 212 AN: 1111256

Other (OTH) AF: 0.00371 AC: 224 AN: 60356

GnomAD4 genome AF: 0.0144 AC: 2187 AN: 152306 Hom.: 57 Cov.: 33 AF XY: 0.0137 AC XY: 1021 AN XY: 74468

African (AFR) AF: 0.0486 AC: 2020 AN: 41564

American (AMR) AF: 0.00615 AC: 94 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68026

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.0131 Hom.: 31

Bravo AF: 0.0161

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs61760955; hg19: chr12-123793863;