5-22756289-G-A

Variant names:

• chr5-22756289-G-A
• rs17358685
• NM_004061.5:c.-523+96769C>T

Variant summary

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

The NM_004061.5(CDH12):​c.-523+96769C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,714 control chromosomes in the GnomAD database, including 4,309 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 0.23 (4309 hom., cov: 31)
• Consequence: CDH12 NM_004061.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 2 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]

ENSG00000286961 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.284 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.-523+96769C>T		intron	N/A	NP_004052.2
	CDH12	NM_001364104.2		c.-428+96769C>T		intron	N/A	NP_001351033.1
	CDH12	NM_001364105.2		c.-523+54328C>T		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.-523+96769C>T		intron	N/A	ENSP00000371689.1
	CDH12	ENST00000504376.6	TSL:5	c.-428+96769C>T		intron	N/A	ENSP00000423577.1
	ENSG00000286961	ENST00000659392.4		n.379-762G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34130 AN: 151594 Hom.: 4307 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.225 AC: 34144 AN: 151714 Hom.: 4309 Cov.: 31 AF XY: 0.225 AC XY: 16680 AN XY: 74122

African (AFR) AF: 0.109 AC: 4516 AN: 41442

American (AMR) AF: 0.237 AC: 3607 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3470

East Asian (EAS) AF: 0.133 AC: 687 AN: 5158

South Asian (SAS) AF: 0.287 AC: 1384 AN: 4814

European-Finnish (FIN) AF: 0.267 AC: 2798 AN: 10482

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.288 AC: 19509 AN: 67822

Other (OTH) AF: 0.236 AC: 496 AN: 2104

Alfa AF: 0.256 Hom.: 5466

Bravo AF: 0.216

Asia WGS AF: 0.184 AC: 636 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.89
DANN	Benign	0.54
PhyloP100		-0.26
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: rs17358685; hg19: chr5-22756398;