chr19-35333116-C-G

Variant names:

• chr19-35333116-C-G
• rs10419538
• NM_001771.4:c.412+192C>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.412+192C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 565,708 control chromosomes in the GnomAD database, including 5,202 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 0.12 (1215 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3987 hom.)
• Consequence: CD22 NM_001771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD22	NM_001771.4	c.412+192C>G		intron_variant	Intron 3 of 13	ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.412+192C>G		intron_variant	Intron 3 of 13	1	NM_001771.4	ENSP00000085219.4

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17604 AN: 152142 Hom.: 1217 Cov.: 32

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.131 AC: 54168 AN: 413448 Hom.: 3987 Cov.: 5 AF XY: 0.127 AC XY: 27204 AN XY: 214138

African (AFR) AF: 0.0523 AC: 635 AN: 12144

American (AMR) AF: 0.146 AC: 2372 AN: 16300

Ashkenazi Jewish (ASJ) AF: 0.0991 AC: 1286 AN: 12972

East Asian (EAS) AF: 0.211 AC: 6351 AN: 30092

South Asian (SAS) AF: 0.0334 AC: 1087 AN: 32514

European-Finnish (FIN) AF: 0.136 AC: 3806 AN: 28074

Middle Eastern (MID) AF: 0.106 AC: 200 AN: 1888

European-Non Finnish (NFE) AF: 0.138 AC: 35192 AN: 254822

Other (OTH) AF: 0.131 AC: 3239 AN: 24642

GnomAD4 genome AF: 0.116 AC: 17590 AN: 152260 Hom.: 1215 Cov.: 32 AF XY: 0.117 AC XY: 8698 AN XY: 74452

African (AFR) AF: 0.0544 AC: 2263 AN: 41562

American (AMR) AF: 0.160 AC: 2446 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0919 AC: 319 AN: 3470

East Asian (EAS) AF: 0.193 AC: 996 AN: 5174

South Asian (SAS) AF: 0.0363 AC: 175 AN: 4826

European-Finnish (FIN) AF: 0.140 AC: 1486 AN: 10612

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9375 AN: 68008

Other (OTH) AF: 0.123 AC: 261 AN: 2114

Alfa AF: 0.121 Hom.: 161

Bravo AF: 0.116

Asia WGS AF: 0.105 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.73
PhyloP100		-0.35
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: rs10419538; hg19: chr19-35824019;