rs7248108

Variant names:

• chr19-35338478-A-G
• rs7248108
• NM_001771.4:c.1249+47A>G

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+47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 1,578,330 control chromosomes in the GnomAD database, including 3,504 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 0.094 (1410 hom., cov: 32)
  • Exomes 𝑓: 0.039 (2094 hom.)
• Consequence: CD22 NM_001771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.886
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 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.1249+47A>G		intron	N/A	NP_001762.2	P20273-1
	CD22	NM_001185099.2		c.985+457A>G		intron	N/A	NP_001172028.1	P20273-3
	CD22	NM_001185100.2		c.1249+47A>G		intron	N/A	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.1249+47A>G		intron	N/A	ENSP00000085219.4	P20273-1
	CD22	ENST00000536635.6	TSL:1	c.985+457A>G		intron	N/A	ENSP00000442279.1	P20273-3
	CD22	ENST00000544992.6	TSL:1	c.1249+47A>G		intron	N/A	ENSP00000441237.1	P20273-4

Frequencies

GnomAD3 genomes AF: 0.0943 AC: 14323 AN: 151966 Hom.: 1410 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0424

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0649

Gnomad FIN AF: 0.0216

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.0570

GnomAD2 exomes AF: 0.0555 AC: 12336 AN: 222202 AF XY: 0.0525

Gnomad AFR exome AF: 0.255

Gnomad AMR exome AF: 0.0267

Gnomad ASJ exome AF: 0.0257

Gnomad EAS exome AF: 0.147

Gnomad FIN exome AF: 0.0213

Gnomad NFE exome AF: 0.0274

Gnomad OTH exome AF: 0.0335

GnomAD4 exome AF: 0.0388 AC: 55363 AN: 1426248 Hom.: 2094 Cov.: 31 AF XY: 0.0386 AC XY: 27194 AN XY: 705350

African (AFR) AF: 0.246 AC: 8031 AN: 32654

American (AMR) AF: 0.0270 AC: 1139 AN: 42224

Ashkenazi Jewish (ASJ) AF: 0.0223 AC: 532 AN: 23848

East Asian (EAS) AF: 0.113 AC: 4430 AN: 39376

South Asian (SAS) AF: 0.0576 AC: 4630 AN: 80366

European-Finnish (FIN) AF: 0.0236 AC: 1219 AN: 51554

Middle Eastern (MID) AF: 0.0201 AC: 113 AN: 5634

European-Non Finnish (NFE) AF: 0.0298 AC: 32503 AN: 1091692

Other (OTH) AF: 0.0470 AC: 2766 AN: 58900

GnomAD4 genome AF: 0.0944 AC: 14350 AN: 152082 Hom.: 1410 Cov.: 32 AF XY: 0.0929 AC XY: 6909 AN XY: 74350

African (AFR) AF: 0.248 AC: 10280 AN: 41438

American (AMR) AF: 0.0424 AC: 648 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3472

East Asian (EAS) AF: 0.141 AC: 723 AN: 5132

South Asian (SAS) AF: 0.0651 AC: 314 AN: 4820

European-Finnish (FIN) AF: 0.0216 AC: 229 AN: 10616

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0286 AC: 1943 AN: 68002

Other (OTH) AF: 0.0588 AC: 124 AN: 2110

Alfa AF: 0.0480 Hom.: 710

Bravo AF: 0.101

Asia WGS AF: 0.112 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.39
PhyloP100		-0.89
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: rs7248108; hg19: chr19-35829381; COSMIC: COSV50054545; COSMIC: COSV50054545;