chr19-35341083-C-T

Variant names:

• chr19-35341083-C-T
• rs25677
• NM_001771.4:c.1452C>T

Variant summary

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

The NM_001771.4(CD22):​c.1452C>T​(p.Cys484Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,614,114 control chromosomes in the GnomAD database, including 1,206 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 0.054 (572 hom., cov: 31)
  • Exomes 𝑓: 0.014 (634 hom.)
• Consequence: CD22 NM_001771.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.819
• Publications: 5 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-0.819 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD22	NM_001771.4	MANE Select	c.1452C>T	p.Cys484Cys	synonymous	Exon 7 of 14	NP_001762.2	P20273-1
	CD22	NM_001185099.2		c.1188C>T	p.Cys396Cys	synonymous	Exon 6 of 13	NP_001172028.1	P20273-3
	CD22	NM_001185100.2		c.1452C>T	p.Cys484Cys	synonymous	Exon 7 of 13	NP_001172029.1	P20273-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD22	ENST00000085219.10	TSL:1 MANE Select	c.1452C>T	p.Cys484Cys	synonymous	Exon 7 of 14	ENSP00000085219.4	P20273-1
	CD22	ENST00000536635.6	TSL:1	c.1188C>T	p.Cys396Cys	synonymous	Exon 6 of 13	ENSP00000442279.1	P20273-3
	CD22	ENST00000544992.6	TSL:1	c.1452C>T	p.Cys484Cys	synonymous	Exon 7 of 13	ENSP00000441237.1	P20273-4

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 8243 AN: 152110 Hom.: 562 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0469

GnomAD2 exomes AF: 0.0205 AC: 5164 AN: 251456 AF XY: 0.0172

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.0166

Gnomad ASJ exome AF: 0.0366

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00323

Gnomad NFE exome AF: 0.0109

Gnomad OTH exome AF: 0.0197

GnomAD4 exome AF: 0.0144 AC: 21106 AN: 1461886 Hom.: 634 Cov.: 33 AF XY: 0.0138 AC XY: 10046 AN XY: 727244

African (AFR) AF: 0.176 AC: 5893 AN: 33478

American (AMR) AF: 0.0178 AC: 797 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0368 AC: 963 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00188 AC: 162 AN: 86258

European-Finnish (FIN) AF: 0.00344 AC: 184 AN: 53420

Middle Eastern (MID) AF: 0.0170 AC: 98 AN: 5768

European-Non Finnish (NFE) AF: 0.0105 AC: 11726 AN: 1112006

Other (OTH) AF: 0.0212 AC: 1282 AN: 60396

GnomAD4 genome AF: 0.0545 AC: 8290 AN: 152228 Hom.: 572 Cov.: 31 AF XY: 0.0531 AC XY: 3949 AN XY: 74438

African (AFR) AF: 0.164 AC: 6791 AN: 41504

American (AMR) AF: 0.0313 AC: 479 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0377 AC: 131 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4822

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10614

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0111 AC: 752 AN: 68024

Other (OTH) AF: 0.0464 AC: 98 AN: 2110

Alfa AF: 0.0290 Hom.: 124

Bravo AF: 0.0615

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.0110

EpiControl AF: 0.0119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.76
DANN	Benign	0.76
PhyloP100		-0.82
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: rs25677; hg19: chr19-35831986;