rs3904166

Positions:

• chr20-46244782-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021248.3(CDH22):​c.256-3525C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,036 control chromosomes in the GnomAD database, including 6,135 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 0.28 (6135 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH22	NM_021248.3	c.256-3525C>A		intron_variant		ENST00000537909.4	NP_067071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH22	ENST00000537909.4	c.256-3525C>A		intron_variant		2	NM_021248.3	ENSP00000437790.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42456 AN: 151918 Hom.: 6136 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.279 AC: 42475 AN: 152036 Hom.: 6135 Cov.: 32 AF XY: 0.277 AC XY: 20608 AN XY: 74328

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.270

Alfa AF: 0.245 Hom.: 9465

Bravo AF: 0.282

Asia WGS AF: 0.235 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs3904166; hg19: chr20-44873421;