chr5-22598137-G-C

Variant names:

• chr5-22598137-G-C
• rs10520880
• NM_004061.5:c.-522-92773C>G

Variant summary

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

The NM_004061.5(CDH12):​c.-522-92773C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 152,150 control chromosomes in the GnomAD database, including 452 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 0.069 (452 hom., cov: 33)
• Consequence: CDH12 NM_004061.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497
• Publications: 1 publications found

Genes affected

CDH12 (HGNC:1751): (cadherin 12) This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature cadherin protein. These integral membrane proteins mediate calcium-dependent cell-cell adhesion and are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. Type II (atypical) cadherins are defined based on their lack of a histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. This particular cadherin appears to be expressed specifically in the brain and its temporal pattern of expression would be consistent with a role during a critical period of neuronal development, perhaps specifically during synaptogenesis. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004061.5. 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
	CDH12	NM_004061.5	MANE Select	c.-522-92773C>G		intron	N/A	NP_004052.2
	CDH12	NM_001364104.2		c.-427-92773C>G		intron	N/A	NP_001351033.1
	CDH12	NM_001364105.2		c.-522-92773C>G		intron	N/A	NP_001351034.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH12	ENST00000382254.6	TSL:1 MANE Select	c.-522-92773C>G		intron	N/A	ENSP00000371689.1
	CDH12	ENST00000504376.6	TSL:5	c.-427-92773C>G		intron	N/A	ENSP00000423577.1
	CDH12	ENST00000520668.1	TSL:4	n.297+40561C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0692 AC: 10522 AN: 152032 Hom.: 451 Cov.: 33

Gnomad AFR AF: 0.0471

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.0878

Gnomad ASJ AF: 0.0866

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.0719

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0647

Gnomad OTH AF: 0.0872

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

GnomAD4 genome AF: 0.0692 AC: 10534 AN: 152150 Hom.: 452 Cov.: 33 AF XY: 0.0696 AC XY: 5178 AN XY: 74366

African (AFR) AF: 0.0473 AC: 1964 AN: 41532

American (AMR) AF: 0.0882 AC: 1346 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0866 AC: 300 AN: 3464

East Asian (EAS) AF: 0.238 AC: 1226 AN: 5162

South Asian (SAS) AF: 0.0348 AC: 168 AN: 4824

European-Finnish (FIN) AF: 0.0719 AC: 761 AN: 10580

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0647 AC: 4402 AN: 68008

Other (OTH) AF: 0.0863 AC: 182 AN: 2108

Alfa AF: 0.0635 Hom.: 30

Bravo AF: 0.0760

Asia WGS AF: 0.104 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.37
DANN	Benign	0.60
PhyloP100		-0.50
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: rs10520880; hg19: chr5-22598246;