rs4805119

chr19-35345848-A-Gchr19-35345848-A-T

Variant summary

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

The NM_001771.4(CD22):c.2327+128A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 721,306 control chromosomes in the GnomAD database, including 43,016 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 (7620 hom., cov: 32)
  • Exomes 𝑓: 0.35 (35396 hom.)
• Consequence: CD22 NM_001771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD22	NM_001771.4	c.2327+128A>G		intron_variant		ENST00000085219.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD22	ENST00000085219.10	c.2327+128A>G		intron_variant		1	NM_001771.4	P2

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47593 AN: 151938 Hom.: 7610 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.347 AC: 197355 AN: 569250 Hom.: 35396 AF XY: 0.355 AC XY: 107508 AN XY: 302770

Gnomad4 AFR exome AF: 0.270

Gnomad4 AMR exome AF: 0.402

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.348

Gnomad4 SAS exome AF: 0.516

Gnomad4 FIN exome AF: 0.328

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.329

GnomAD4 genome AF: 0.313 AC: 47633 AN: 152056 Hom.: 7620 Cov.: 32 AF XY: 0.318 AC XY: 23632 AN XY: 74332

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.295

Alfa AF: 0.314 Hom.: 6232

Bravo AF: 0.309

Asia WGS AF: 0.405 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.8
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs4805119; hg19: chr19-35836751;