chr19-35345848-A-G

Variant names:

• chr19-35345848-A-G
• rs4805119
• NM_001771.4:c.2327+128A>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.2327+128A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 721,306 control chromosomes in the GnomAD database, including 43,016 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 0.31 (7620 hom., cov: 32)
  • Exomes 𝑓: 0.35 (35396 hom.)
• Consequence: CD22 NM_001771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826
• 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]

MIR5196 (HGNC:43542): (microRNA 5196) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 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.2327+128A>G		intron	N/A	NP_001762.2	P20273-1
	CD22	NM_001185099.2		c.2063+128A>G		intron	N/A	NP_001172028.1	P20273-3
	CD22	NM_001185100.2		c.2209-303A>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.2327+128A>G		intron	N/A	ENSP00000085219.4	P20273-1
	CD22	ENST00000536635.6	TSL:1	c.2063+128A>G		intron	N/A	ENSP00000442279.1	P20273-3
	CD22	ENST00000544992.6	TSL:1	c.2209-303A>G		intron	N/A	ENSP00000441237.1	P20273-4

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47593 AN: 151938 Hom.: 7610 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.347 AC: 197355 AN: 569250 Hom.: 35396 AF XY: 0.355 AC XY: 107508 AN XY: 302770

African (AFR) AF: 0.270 AC: 4201 AN: 15536

American (AMR) AF: 0.402 AC: 11612 AN: 28876

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 5364 AN: 15394

East Asian (EAS) AF: 0.348 AC: 12189 AN: 35004

South Asian (SAS) AF: 0.516 AC: 28676 AN: 55582

European-Finnish (FIN) AF: 0.328 AC: 13689 AN: 41778

Middle Eastern (MID) AF: 0.331 AC: 1242 AN: 3752

European-Non Finnish (NFE) AF: 0.322 AC: 110420 AN: 343094

Other (OTH) AF: 0.329 AC: 9962 AN: 30234

GnomAD4 genome AF: 0.313 AC: 47633 AN: 152056 Hom.: 7620 Cov.: 32 AF XY: 0.318 AC XY: 23632 AN XY: 74332

African (AFR) AF: 0.272 AC: 11296 AN: 41500

American (AMR) AF: 0.334 AC: 5103 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1212 AN: 3466

East Asian (EAS) AF: 0.322 AC: 1661 AN: 5166

South Asian (SAS) AF: 0.478 AC: 2306 AN: 4822

European-Finnish (FIN) AF: 0.321 AC: 3394 AN: 10564

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21748 AN: 67948

Other (OTH) AF: 0.295 AC: 623 AN: 2114

Alfa AF: 0.313 Hom.: 7427

Bravo AF: 0.309

Asia WGS AF: 0.405 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.41
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4805119;

hg19: chr19-35836751;