chr19-35347173-C-T

Position:

• chr19-35347173-C-T

Variant summary

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

The ENST00000085219.10(CD22):​c.*476C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0849 in 155,996 control chromosomes in the GnomAD database, including 668 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 0.085 (642 hom., cov: 32)
  • Exomes 𝑓: 0.072 (26 hom.)
• Consequence: CD22 ENST00000085219.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD22	NM_001771.4	c.*476C>T		3_prime_UTR_variant	14/14	ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.*476C>T		3_prime_UTR_variant	14/14	1	NM_001771.4	ENSP00000085219	P2
CD22	ENST00000536635.6	c.*476C>T		3_prime_UTR_variant	13/13	1		ENSP00000442279
CD22	ENST00000341773.10	c.*476C>T		3_prime_UTR_variant	12/12	5		ENSP00000339349
CD22	ENST00000601769.5	c.*2325C>T		3_prime_UTR_variant, NMD_transcript_variant	14/14	2		ENSP00000470193

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12922 AN: 152032 Hom.: 630 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.0542

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0645

Gnomad OTH AF: 0.0742

GnomAD4 exome AF: 0.0718 AC: 276 AN: 3844 Hom.: 26 Cov.: 0 AF XY: 0.0864 AC XY: 181 AN XY: 2094

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.0380

Gnomad4 ASJ exome AF: 0.0385

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.0313

Gnomad4 NFE exome AF: 0.0484

Gnomad4 OTH exome AF: 0.0435

GnomAD4 genome AF: 0.0852 AC: 12966 AN: 152152 Hom.: 642 Cov.: 32 AF XY: 0.0873 AC XY: 6495 AN XY: 74378

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0563

Gnomad4 ASJ AF: 0.0671

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.0542

Gnomad4 NFE AF: 0.0645

Gnomad4 OTH AF: 0.0820

Alfa AF: 0.0665 Hom.: 404

Bravo AF: 0.0835

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.8
DANN	Benign	0.61

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: rs3088063; hg19: chr19-35838076;