Genetic Variant CD22:c.412+172C>T (chr19-35333096-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001771.4(CD22):c.412+172C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 618,712 control chromosomes in the GnomAD database, including 222 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 0.019 ( 43 hom., cov: 32)

Exomes 𝑓: 0.022 ( 179 hom. )

Consequence

CD22
NM_001771.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.489

Publications

1 publications found

Variant links:

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]

CD22 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.019 (2897/152290) while in subpopulation NFE AF = 0.0267 (1818/68018). AF 95% confidence interval is 0.0257. There are 43 homozygotes in GnomAd4. There are 1507 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD22	NM_001771.4 link	c.412+172C>T		intron_variant	Intron 3 of 13	ENST00000085219.10	NP_001762.2	P20273-1Q0EAF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10 link	c.412+172C>T		intron_variant	Intron 3 of 13	1	NM_001771.4	ENSP00000085219.4		P20273-1

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2898

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00352

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.0586

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0267

Gnomad OTH

AF:

0.0134

GnomAD4 exome

AF:

0.0224

AC:

10438

AN:

466422

Hom.:

179

Cov.:

AF XY:

0.0224

AC XY:

5388

AN XY:

241006

show subpopulations

African (AFR)

AF:

0.00374

AC:

AN:

13114

American (AMR)

AF:

0.00702

AC:

121

AN:

17226

Ashkenazi Jewish (ASJ)

AF:

0.0205

AC:

274

AN:

13362

East Asian (EAS)

AF:

0.0000980

AC:

AN:

30612

South Asian (SAS)

AF:

0.0175

AC:

624

AN:

35642

European-Finnish (FIN)

AF:

0.0478

AC:

1377

AN:

28814

Middle Eastern (MID)

AF:

0.0255

AC:

AN:

1960

European-Non Finnish (NFE)

AF:

0.0247

AC:

7395

AN:

299188

Other (OTH)

AF:

0.0206

AC:

545

AN:

26504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

487

974

1460

1947

2434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0190

AC:

2897

AN:

152290

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

1507

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00351

AC:

146

AN:

41564

American (AMR)

AF:

0.00739

AC:

113

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0213

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.0170

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0586

AC:

622

AN:

10612

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0267

AC:

1818

AN:

68018

Other (OTH)

AF:

0.0128

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

143

287

430

574

717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0223

Hom.:

Bravo

AF:

0.0146

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.8

(source)

DANN

Benign

0.90

PhyloP100

-0.49

Mutation Taster

=100/0

polymorphism

(source)

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

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19-35333096-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over