19-35338610-T-C

Position:

• chr19-35338610-T-C

Variant summary

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

The NM_001771.4(CD22):​c.1249+179T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 151,830 control chromosomes in the GnomAD database, including 49,380 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 0.80 (49380 hom., cov: 28)
• Consequence: CD22 NM_001771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD22	NM_001771.4	c.1249+179T>C		intron_variant		ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.1249+179T>C		intron_variant		1	NM_001771.4	ENSP00000085219	P2

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121304 AN: 151712 Hom.: 49314 Cov.: 28

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.817

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.800 AC: 121431 AN: 151830 Hom.: 49380 Cov.: 28 AF XY: 0.799 AC XY: 59247 AN XY: 74172

Gnomad4 AFR AF: 0.944

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.893

Gnomad4 SAS AF: 0.867

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.819

Alfa AF: 0.742 Hom.: 51397

Bravo AF: 0.810

Asia WGS AF: 0.895 AC: 3112 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	2.1
DANN	Benign	0.86

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: rs7251526; hg19: chr19-35829513;