rs1321001

Variant names:

• chr20-46188097-T-G
• rs1321001
• NM_021248.3:c.1424-1150A>C

Variant summary

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

The NM_021248.3(CDH22):​c.1424-1150A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,066 control chromosomes in the GnomAD database, including 7,929 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 (7929 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH22	NM_021248.3	c.1424-1150A>C		intron_variant	Intron 8 of 11	ENST00000537909.4	NP_067071.1
CDH22	XM_011528994.3	c.1424-1150A>C		intron_variant	Intron 8 of 11		XP_011527296.1
CDH22	XM_047440373.1	c.1424-9900A>C		intron_variant	Intron 8 of 9		XP_047296329.1
CDH22	XM_024451966.2	c.1061-1150A>C		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.1424-1150A>C		intron_variant	Intron 8 of 11	2	NM_021248.3	ENSP00000437790.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42139 AN: 151948 Hom.: 7914 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.278 AC: 42206 AN: 152066 Hom.: 7929 Cov.: 32 AF XY: 0.277 AC XY: 20620 AN XY: 74340

African (AFR) AF: 0.532 AC: 22053 AN: 41418

American (AMR) AF: 0.262 AC: 3999 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0836 AC: 290 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1905 AN: 5176

South Asian (SAS) AF: 0.183 AC: 881 AN: 4820

European-Finnish (FIN) AF: 0.162 AC: 1714 AN: 10596

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10646 AN: 67988

Other (OTH) AF: 0.253 AC: 535 AN: 2112

Alfa AF: 0.195 Hom.: 16785

Bravo AF: 0.299

Asia WGS AF: 0.318 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	9.5
DANN	Benign	0.71
PhyloP100		1.1
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: rs1321001; hg19: chr20-44816736;