rs6017767

Variant names:

• chr20-46303290-C-G
• rs6017767
• NM_021248.3:c.-400+4965G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-46303290-C-G
• chr20-46303290-C-T

Variant summary

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

The ENST00000537909.4(CDH22):​c.-400+4965G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,076 control chromosomes in the GnomAD database, including 12,990 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 0.40 (12990 hom., cov: 32)
• Consequence: CDH22 ENST00000537909.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000537909.4. 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.-400+4965G>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.-400+4965G>C		intron	N/A	ENSP00000437790.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60962 AN: 151958 Hom.: 12995 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.401 AC: 60965 AN: 152076 Hom.: 12990 Cov.: 32 AF XY: 0.404 AC XY: 30013 AN XY: 74328

African (AFR) AF: 0.235 AC: 9749 AN: 41490

American (AMR) AF: 0.419 AC: 6401 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1570 AN: 3470

East Asian (EAS) AF: 0.524 AC: 2704 AN: 5162

South Asian (SAS) AF: 0.430 AC: 2073 AN: 4816

European-Finnish (FIN) AF: 0.506 AC: 5344 AN: 10564

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31644 AN: 67978

Other (OTH) AF: 0.402 AC: 849 AN: 2110

Alfa AF: 0.298 Hom.: 876

Bravo AF: 0.388

Asia WGS AF: 0.419 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.52
PhyloP100		-0.011
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6017767; hg19: chr20-44931929;