NM_001771.4:c.2327+147G>A

Variant names:

• chr19-35345867-G-A
• rs10406539
• NM_001771.4:c.2327+147G>A

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+147G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 685,932 control chromosomes in the GnomAD database, including 10,246 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 0.16 (2263 hom., cov: 32)
  • Exomes 𝑓: 0.16 (7983 hom.)
• Consequence: CD22 NM_001771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD22	NM_001771.4	c.2327+147G>A		intron_variant	Intron 12 of 13	ENST00000085219.10	NP_001762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD22	ENST00000085219.10	c.2327+147G>A		intron_variant	Intron 12 of 13	1	NM_001771.4	ENSP00000085219.4

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24890 AN: 152104 Hom.: 2254 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0570

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.158 AC: 84498 AN: 533710 Hom.: 7983 AF XY: 0.167 AC XY: 47501 AN XY: 284754

African (AFR) AF: 0.215 AC: 3183 AN: 14806

American (AMR) AF: 0.227 AC: 6054 AN: 26720

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 3076 AN: 14992

East Asian (EAS) AF: 0.0842 AC: 2878 AN: 34168

South Asian (SAS) AF: 0.322 AC: 17446 AN: 54116

European-Finnish (FIN) AF: 0.121 AC: 4749 AN: 39122

Middle Eastern (MID) AF: 0.224 AC: 796 AN: 3554

European-Non Finnish (NFE) AF: 0.132 AC: 41704 AN: 317138

Other (OTH) AF: 0.159 AC: 4612 AN: 29094

GnomAD4 genome AF: 0.164 AC: 24929 AN: 152222 Hom.: 2263 Cov.: 32 AF XY: 0.166 AC XY: 12354 AN XY: 74440

African (AFR) AF: 0.212 AC: 8823 AN: 41542

American (AMR) AF: 0.180 AC: 2750 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3472

East Asian (EAS) AF: 0.0573 AC: 297 AN: 5180

South Asian (SAS) AF: 0.292 AC: 1408 AN: 4820

European-Finnish (FIN) AF: 0.120 AC: 1275 AN: 10610

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9090 AN: 67986

Other (OTH) AF: 0.165 AC: 347 AN: 2108

Alfa AF: 0.146 Hom.: 4591

Bravo AF: 0.167

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.6
DANN	Benign	0.54
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs10406539; hg19: chr19-35836770;