20-46246056-T-G

Variant names:

• chr20-46246056-T-G
• rs3848729
• NM_021248.3:c.256-4799A>C

Variant summary

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

The NM_021248.3(CDH22):​c.256-4799A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,038 control chromosomes in the GnomAD database, including 30,696 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 0.63 (30696 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH22	NM_021248.3	c.256-4799A>C		intron_variant	Intron 2 of 11	ENST00000537909.4	NP_067071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH22	ENST00000537909.4	c.256-4799A>C		intron_variant	Intron 2 of 11	2	NM_021248.3	ENSP00000437790.1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96315 AN: 151920 Hom.: 30667 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.634 AC: 96383 AN: 152038 Hom.: 30696 Cov.: 32 AF XY: 0.636 AC XY: 47237 AN XY: 74320

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.707

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.607

Alfa AF: 0.610 Hom.: 3343

Bravo AF: 0.622

Asia WGS AF: 0.611 AC: 2126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.74

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: rs3848729; hg19: chr20-44874695;