rs761048

Variant names:

• chr20-46222418-C-G
• rs761048
• NM_021248.3:c.670+5090G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-46222418-C-G
• chr20-46222418-C-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.670+5090G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 152,278 control chromosomes in the GnomAD database, including 65,961 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 0.93 (65961 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.955 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.670+5090G>C		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.670+5090G>C		intron	N/A	ENSP00000437790.1

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141407 AN: 152160 Hom.: 65907 Cov.: 32

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.929

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.928

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

GnomAD4 genome AF: 0.929 AC: 141518 AN: 152278 Hom.: 65961 Cov.: 32 AF XY: 0.928 AC XY: 69064 AN XY: 74452

African (AFR) AF: 0.963 AC: 39996 AN: 41534

American (AMR) AF: 0.885 AC: 13546 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 3224 AN: 3472

East Asian (EAS) AF: 0.733 AC: 3795 AN: 5178

South Asian (SAS) AF: 0.877 AC: 4230 AN: 4822

European-Finnish (FIN) AF: 0.970 AC: 10307 AN: 10624

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.932 AC: 63389 AN: 68018

Other (OTH) AF: 0.930 AC: 1966 AN: 2114

Alfa AF: 0.949 Hom.: 3221

Bravo AF: 0.924

Asia WGS AF: 0.829 AC: 2882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.59
PhyloP100		0.31
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: rs761048; hg19: chr20-44851057;