rs45453699

Variant names:

• chr19-35345037-C-T
• rs45453699
• NM_001771.4:c.2133-14C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001771.4(CD22):​c.2133-14C>T variant causes a 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001771.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD22	NM_001771.4	MANE Select	c.2133-14C>T		intron	N/A	NP_001762.2
	CD22	NM_001185099.2		c.1869-14C>T		intron	N/A	NP_001172028.1
	CD22	NM_001185100.2		c.2133-14C>T		intron	N/A	NP_001172029.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD22	ENST00000085219.10	TSL:1 MANE Select	c.2133-14C>T		intron	N/A	ENSP00000085219.4
	CD22	ENST00000536635.6	TSL:1	c.1869-14C>T		intron	N/A	ENSP00000442279.1
	CD22	ENST00000544992.6	TSL:1	c.2133-14C>T		intron	N/A	ENSP00000441237.1

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

GnomAD2 exomes AF: 0.282 AC: 70944 AN: 251452 AF XY: 0.275

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 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

African (AFR) AF: 0.415 AC: 13869 AN: 33422

American (AMR) AF: 0.361 AC: 16122 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 7483 AN: 26112

East Asian (EAS) AF: 0.296 AC: 11766 AN: 39690

South Asian (SAS) AF: 0.230 AC: 19812 AN: 86190

European-Finnish (FIN) AF: 0.212 AC: 11318 AN: 53408

Middle Eastern (MID) AF: 0.346 AC: 1993 AN: 5762

European-Non Finnish (NFE) AF: 0.263 AC: 291851 AN: 1109816

Other (OTH) AF: 0.278 AC: 16738 AN: 60310

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

African (AFR) AF: 0.410 AC: 16994 AN: 41424

American (AMR) AF: 0.365 AC: 5567 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 999 AN: 3468

East Asian (EAS) AF: 0.278 AC: 1430 AN: 5152

South Asian (SAS) AF: 0.255 AC: 1227 AN: 4814

European-Finnish (FIN) AF: 0.209 AC: 2205 AN: 10560

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.271 AC: 18416 AN: 67950

Other (OTH) AF: 0.334 AC: 704 AN: 2108

Alfa AF: 0.298 Hom.: 3389

Bravo AF: 0.332

Asia WGS AF: 0.251 AC: 870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.41
DANN	Benign	0.48
PhyloP100		-1.7
Mutation Taster		=100/0	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: rs45453699; hg19: chr19-35835940;