20-46191225-T-C

Variant names:

• chr20-46191225-T-C
• rs4383400
• NM_021248.3:c.1424-4278A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021248.3(CDH22):​c.1424-4278A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,948 control chromosomes in the GnomAD database, including 6,169 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 0.20 (6169 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.64
• Publications: 5 publications found

Genes affected

CDH22 (HGNC:13251): (cadherin 22) This gene is a member of the cadherin superfamily. The gene product is composed of five cadherin repeat domains and a cytoplasmic tail similar to the highly conserved cytoplasmic region of classical cadherins. Expressed predominantly in the brain, this putative calcium-dependent cell adhesion protein may play an important role in morphogenesis and tissue formation in neural and non-neural cells during development and maintenance of the brain and neuroendocrine organs. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH22	NM_021248.3	c.1424-4278A>G		intron_variant	Intron 8 of 11	ENST00000537909.4	NP_067071.1
CDH22	XM_011528994.3	c.1424-4278A>G		intron_variant	Intron 8 of 11		XP_011527296.1
CDH22	XM_047440373.1	c.1423+8198A>G		intron_variant	Intron 8 of 9		XP_047296329.1
CDH22	XM_024451966.2	c.1061-4278A>G		intron_variant	Intron 8 of 11		XP_024307734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH22	ENST00000537909.4	c.1424-4278A>G		intron_variant	Intron 8 of 11	2	NM_021248.3	ENSP00000437790.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29651 AN: 151830 Hom.: 6143 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0113

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0419

Gnomad OTH AF: 0.153

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.196 AC: 29721 AN: 151948 Hom.: 6169 Cov.: 32 AF XY: 0.195 AC XY: 14480 AN XY: 74276

African (AFR) AF: 0.508 AC: 20970 AN: 41308

American (AMR) AF: 0.151 AC: 2304 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 39 AN: 3454

East Asian (EAS) AF: 0.432 AC: 2226 AN: 5152

South Asian (SAS) AF: 0.137 AC: 658 AN: 4814

European-Finnish (FIN) AF: 0.0237 AC: 252 AN: 10620

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0419 AC: 2852 AN: 67996

Other (OTH) AF: 0.151 AC: 319 AN: 2110

Alfa AF: 0.0809 Hom.: 4204

Bravo AF: 0.223

Asia WGS AF: 0.282 AC: 978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.30
PhyloP100		-3.6
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: rs4383400; hg19: chr20-44819864;