chr12-123321672-C-T

Position:

• chr12-123321672-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001167856.3(SBNO1):​c.2186G>A​(p.Ser729Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,613,612 control chromosomes in the GnomAD database, including 32,584 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (2372 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30212 hom.)
• Consequence: SBNO1 NM_001167856.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.22

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014118552).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBNO1	NM_001167856.3	c.2186G>A	p.Ser729Asn	missense_variant	17/32	ENST00000602398.3
SBNO1	NM_018183.5	c.2183G>A	p.Ser728Asn	missense_variant	17/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBNO1	ENST00000602398.3	c.2186G>A	p.Ser729Asn	missense_variant	17/32	5	NM_001167856.3	P4
SBNO1	ENST00000420886.6	c.2186G>A	p.Ser729Asn	missense_variant	16/31	1		P4
SBNO1	ENST00000267176.8	c.2183G>A	p.Ser728Asn	missense_variant	17/32	5		A1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24718 AN: 152002 Hom.: 2364 Cov.: 32

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.171

GnomAD3 exomes AF: 0.191 AC: 47988 AN: 251348 Hom.: 5345 AF XY: 0.195 AC XY: 26515 AN XY: 135850

Gnomad AFR exome AF: 0.0763

Gnomad AMR exome AF: 0.231

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.00120

Gnomad SAS exome AF: 0.223

Gnomad FIN exome AF: 0.220

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.198 AC: 289508 AN: 1461492 Hom.: 30212 Cov.: 33 AF XY: 0.200 AC XY: 145502 AN XY: 727064

Gnomad4 AFR exome AF: 0.0720

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.000554

Gnomad4 SAS exome AF: 0.226

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.163 AC: 24726 AN: 152120 Hom.: 2372 Cov.: 32 AF XY: 0.164 AC XY: 12219 AN XY: 74354

Gnomad4 AFR AF: 0.0790

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.00424

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.169

Alfa AF: 0.195 Hom.: 8122

Bravo AF: 0.155

TwinsUK AF: 0.200 AC: 742

ALSPAC AF: 0.197 AC: 760

ESP6500AA AF: 0.0824 AC: 363

ESP6500EA AF: 0.197 AC: 1698

ExAC AF: 0.187 AC: 22705

Asia WGS AF: 0.101 AC: 352 AN: 3478

EpiCase AF: 0.216

EpiControl AF: 0.209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T;.;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;.
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.;M
MutationTaster	Benign	0.0000013	P;P
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.43	N;N;.
REVEL	Benign	0.11
Sift	Benign	0.14	T;T;.
Sift4G	Benign	0.65	T;T;T
Polyphen		0.085	B;B;B
Vest4		0.21
MPC		0.67
ClinPred		0.038	T
GERP RS		5.5
Varity_R		0.32
gMVP		0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs1060105; hg19: chr12-123806219; COSMIC: COSV57340080;