rs45453699

Positions:

• chr19-35345037-C-T

Variant summary

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

The NM_001771.4(CD22):​c.2133-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,611,370 control chromosomes in the GnomAD database, including 61,394 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 0.31 (7907 hom., cov: 31)
  • Exomes 𝑓: 0.27 (53487 hom.)
• Consequence: CD22 NM_001771.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

Genes affected

CD22 (HGNC:1643): (CD22 molecule) Predicted to enable CD4 receptor binding activity; protein phosphatase binding activity; and sialic acid binding activity. Involved in B cell activation; negative regulation of B cell receptor signaling pathway; and regulation of endocytosis. Located in early endosome and recycling endosome. [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 (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD22	NM_001771.4	c.2133-14C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.2133-14C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001771.4	ENSP00000085219	P2

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47791 AN: 151824 Hom.: 7898 Cov.: 31

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.338

GnomAD3 exomes AF: 0.282 AC: 70944 AN: 251452 Hom.: 10434 AF XY: 0.275 AC XY: 37400 AN XY: 135896

Gnomad AFR exome AF: 0.417

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.266

Gnomad SAS exome AF: 0.230

Gnomad FIN exome AF: 0.216

Gnomad NFE exome AF: 0.268

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.268 AC: 390952 AN: 1459428 Hom.: 53487 Cov.: 31 AF XY: 0.267 AC XY: 193741 AN XY: 726210

Gnomad4 AFR exome AF: 0.415

Gnomad4 AMR exome AF: 0.361

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.296

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.315 AC: 47832 AN: 151942 Hom.: 7907 Cov.: 31 AF XY: 0.310 AC XY: 23043 AN XY: 74242

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.334

Alfa AF: 0.293 Hom.: 2210

Bravo AF: 0.332

Asia WGS AF: 0.251 AC: 870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.41
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs45453699; hg19: chr19-35835940;