20-46227824-G-A

Variant names:

• chr20-46227824-G-A
• rs733379
• NM_021248.3:c.551-197C>T

Variant summary

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

The NM_021248.3(CDH22):​c.551-197C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,060 control chromosomes in the GnomAD database, including 8,609 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 0.32 (8609 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021248.3. 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
	CDH22	NM_021248.3	MANE Select	c.551-197C>T		intron	N/A	NP_067071.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH22	ENST00000537909.4	TSL:2 MANE Select	c.551-197C>T		intron	N/A	ENSP00000437790.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47986 AN: 151942 Hom.: 8601 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.316 AC: 48027 AN: 152060 Hom.: 8609 Cov.: 32 AF XY: 0.312 AC XY: 23216 AN XY: 74306

African (AFR) AF: 0.510 AC: 21136 AN: 41472

American (AMR) AF: 0.244 AC: 3741 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 876 AN: 3472

East Asian (EAS) AF: 0.263 AC: 1352 AN: 5150

South Asian (SAS) AF: 0.278 AC: 1340 AN: 4816

European-Finnish (FIN) AF: 0.258 AC: 2728 AN: 10582

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16008 AN: 67944

Other (OTH) AF: 0.296 AC: 626 AN: 2116

Alfa AF: 0.261 Hom.: 16740

Bravo AF: 0.324

Asia WGS AF: 0.260 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.49
PhyloP100		-1.0
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: rs733379; hg19: chr20-44856463;