NM_001771.4:c.1249+47A>G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD22	NM_001771.4	c.1249+47A>G		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+47A>G		intron_variant	Intron 6 of 13	1	NM_001771.4	ENSP00000085219.4

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

GnomAD3 exomes AF: 0.0555 AC: 12336 AN: 222202 Hom.: 817 AF XY: 0.0525 AC XY: 6273 AN XY: 119494

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 SAS exome AF: 0.0584

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

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.0270

Gnomad4 ASJ exome AF: 0.0223

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.0576

Gnomad4 FIN exome AF: 0.0236

Gnomad4 NFE exome AF: 0.0298

Gnomad4 OTH exome AF: 0.0470

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

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.0424

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.0651

Gnomad4 FIN AF: 0.0216

Gnomad4 NFE AF: 0.0286

Gnomad4 OTH AF: 0.0588

Alfa AF: 0.0712 Hom.: 239

Bravo AF: 0.101

Asia WGS AF: 0.112 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.39

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: rs7248108; hg19: chr19-35829381; COSMIC: COSV50054545; COSMIC: COSV50054545;