NM_001771.4:c.412+172C>T

Variant names:

• chr19-35333096-C-T
• rs881456
• NM_001771.4:c.412+172C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001771.4(CD22):​c.412+172C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 618,712 control chromosomes in the GnomAD database, including 222 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 0.019 (43 hom., cov: 32)
  • Exomes 𝑓: 0.022 (179 hom.)
• Consequence: CD22 NM_001771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• Publications: 1 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).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.019 (2897/152290) while in subpopulation NFE AF = 0.0267 (1818/68018). AF 95% confidence interval is 0.0257. There are 43 homozygotes in GnomAd4. There are 1507 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 43 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD22	NM_001771.4	MANE Select	c.412+172C>T		intron	N/A	NP_001762.2
	CD22	NM_001185099.2		c.412+172C>T		intron	N/A	NP_001172028.1
	CD22	NM_001185100.2		c.412+172C>T		intron	N/A	NP_001172029.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD22	ENST00000085219.10	TSL:1 MANE Select	c.412+172C>T		intron	N/A	ENSP00000085219.4
	CD22	ENST00000536635.6	TSL:1	c.412+172C>T		intron	N/A	ENSP00000442279.1
	CD22	ENST00000544992.6	TSL:1	c.412+172C>T		intron	N/A	ENSP00000441237.1

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2898 AN: 152172 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.00352

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.00740

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0267

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.0224 AC: 10438 AN: 466422 Hom.: 179 Cov.: 6 AF XY: 0.0224 AC XY: 5388 AN XY: 241006

African (AFR) AF: 0.00374 AC: 49 AN: 13114

American (AMR) AF: 0.00702 AC: 121 AN: 17226

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 274 AN: 13362

East Asian (EAS) AF: 0.0000980 AC: 3 AN: 30612

South Asian (SAS) AF: 0.0175 AC: 624 AN: 35642

European-Finnish (FIN) AF: 0.0478 AC: 1377 AN: 28814

Middle Eastern (MID) AF: 0.0255 AC: 50 AN: 1960

European-Non Finnish (NFE) AF: 0.0247 AC: 7395 AN: 299188

Other (OTH) AF: 0.0206 AC: 545 AN: 26504

GnomAD4 genome AF: 0.0190 AC: 2897 AN: 152290 Hom.: 43 Cov.: 32 AF XY: 0.0202 AC XY: 1507 AN XY: 74462

African (AFR) AF: 0.00351 AC: 146 AN: 41564

American (AMR) AF: 0.00739 AC: 113 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4828

European-Finnish (FIN) AF: 0.0586 AC: 622 AN: 10612

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0267 AC: 1818 AN: 68018

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.0223 Hom.: 16

Bravo AF: 0.0146

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.90
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism

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: rs881456; hg19: chr19-35823999;