rs2302109

Variant names:

• chr19-1110830-G-A
• rs2302109
• NM_014963.3:c.2943C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014963.3(SBNO2):​c.2943C>T​(p.Asn981Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,613,160 control chromosomes in the GnomAD database, including 220,398 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.

• Frequency:
  • Genomes: 𝑓 0.57 (24629 hom., cov: 31)
  • Exomes 𝑓: 0.52 (195769 hom.)
• Consequence: SBNO2 NM_014963.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.767
• Publications: 38 publications found

Genes affected

SBNO2 (HGNC:29158): (strawberry notch homolog 2) Predicted to enable chromatin DNA binding activity and histone binding activity. Involved in several processes, including cellular response to interleukin-6; macrophage activation involved in immune response; and negative 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.767 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBNO2	NM_014963.3	c.2943C>T	p.Asn981Asn	synonymous_variant	Exon 26 of 32	ENST00000361757.8	NP_055778.2
SBNO2	NM_001100122.2	c.2772C>T	p.Asn924Asn	synonymous_variant	Exon 23 of 29		NP_001093592.1
SBNO2	XM_011527804.4	c.2943C>T	p.Asn981Asn	synonymous_variant	Exon 26 of 32		XP_011526106.1
SBNO2	XM_047438466.1	c.1746C>T	p.Asn582Asn	synonymous_variant	Exon 23 of 29		XP_047294422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBNO2	ENST00000361757.8	c.2943C>T	p.Asn981Asn	synonymous_variant	Exon 26 of 32	1	NM_014963.3	ENSP00000354733.2

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85921 AN: 151654 Hom.: 24591 Cov.: 31

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.539

GnomAD2 exomes AF: 0.536 AC: 133491 AN: 249062 AF XY: 0.529

Gnomad AFR exome AF: 0.665

Gnomad AMR exome AF: 0.598

Gnomad ASJ exome AF: 0.498

Gnomad EAS exome AF: 0.473

Gnomad FIN exome AF: 0.600

Gnomad NFE exome AF: 0.505

Gnomad OTH exome AF: 0.505

GnomAD4 exome AF: 0.515 AC: 753322 AN: 1461388 Hom.: 195769 Cov.: 55 AF XY: 0.515 AC XY: 374177 AN XY: 727008

African (AFR) AF: 0.662 AC: 22180 AN: 33480

American (AMR) AF: 0.595 AC: 26614 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 12999 AN: 26128

East Asian (EAS) AF: 0.529 AC: 20988 AN: 39690

South Asian (SAS) AF: 0.515 AC: 44420 AN: 86254

European-Finnish (FIN) AF: 0.597 AC: 31849 AN: 53342

Middle Eastern (MID) AF: 0.458 AC: 2639 AN: 5764

European-Non Finnish (NFE) AF: 0.505 AC: 560871 AN: 1111660

Other (OTH) AF: 0.510 AC: 30762 AN: 60360

GnomAD4 genome AF: 0.567 AC: 86015 AN: 151772 Hom.: 24629 Cov.: 31 AF XY: 0.571 AC XY: 42338 AN XY: 74154

African (AFR) AF: 0.663 AC: 27435 AN: 41364

American (AMR) AF: 0.591 AC: 9017 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1724 AN: 3472

East Asian (EAS) AF: 0.472 AC: 2421 AN: 5124

South Asian (SAS) AF: 0.528 AC: 2539 AN: 4810

European-Finnish (FIN) AF: 0.612 AC: 6447 AN: 10536

Middle Eastern (MID) AF: 0.493 AC: 143 AN: 290

European-Non Finnish (NFE) AF: 0.507 AC: 34452 AN: 67910

Other (OTH) AF: 0.543 AC: 1141 AN: 2100

Alfa AF: 0.528 Hom.: 63792

Bravo AF: 0.567

Asia WGS AF: 0.542 AC: 1886 AN: 3478

EpiCase AF: 0.497

EpiControl AF: 0.494

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.3
DANN	Benign	0.79
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2302109; hg19: chr19-1110829; COSMIC: COSV62321060; COSMIC: COSV62321060;