19-35338610-T-C

Variant names:

• chr19-35338610-T-C
• rs7251526
• NM_001771.4:c.1249+179T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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 -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 rank	MANE	Protein	UniProt
CD22	NM_001771.4	c.1249+179T>C		intron_variant	Intron 6 of 13	ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.1249+179T>C		intron_variant	Intron 6 of 13	1	NM_001771.4	ENSP00000085219.4

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

African (AFR) AF: 0.944 AC: 39168 AN: 41474

American (AMR) AF: 0.777 AC: 11855 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2788 AN: 3470

East Asian (EAS) AF: 0.893 AC: 4523 AN: 5066

South Asian (SAS) AF: 0.867 AC: 4155 AN: 4792

European-Finnish (FIN) AF: 0.666 AC: 7017 AN: 10532

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49199 AN: 67924

Other (OTH) AF: 0.819 AC: 1730 AN: 2112

Alfa AF: 0.749 Hom.: 67323

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
PhyloP100		-0.12
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: rs7251526; hg19: chr19-35829513;