rs17358685

chr5-22756289-G-Achr5-22756289-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH12	NM_004061.5	c.-523+96769C>T		intron_variant		ENST00000382254.6
LOC101929617	XR_241750.6	n.301-762G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH12	ENST00000382254.6	c.-523+96769C>T		intron_variant		1	NM_004061.5	P1
	ENST00000660998.1	n.72-762G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.236

Alfa AF: 0.257 Hom.: 4616

Bravo AF: 0.216

Asia WGS AF: 0.184 AC: 636 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.89
Dann	Benign	0.54

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: rs17358685; hg19: chr5-22756398;