rs268972

Variant names:

• chr5-22656418-A-C
• rs268972
• NM_004061.5:c.-522-151054T>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.-522-151054T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,954 control chromosomes in the GnomAD database, including 27,132 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 0.59 (27132 hom., cov: 32)
• Consequence: CDH12 NM_004061.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• 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]

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 = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH12	NM_004061.5	c.-522-151054T>G		intron_variant	Intron 1 of 14	ENST00000382254.6	NP_004052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH12	ENST00000382254.6	c.-522-151054T>G		intron_variant	Intron 1 of 14	1	NM_004061.5	ENSP00000371689.1
CDH12	ENST00000504376.6	c.-427-151054T>G		intron_variant	Intron 1 of 13	5		ENSP00000423577.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89817 AN: 151836 Hom.: 27107 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.592 AC: 89898 AN: 151954 Hom.: 27132 Cov.: 32 AF XY: 0.598 AC XY: 44366 AN XY: 74248

African (AFR) AF: 0.662 AC: 27430 AN: 41424

American (AMR) AF: 0.660 AC: 10081 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1665 AN: 3470

East Asian (EAS) AF: 0.867 AC: 4474 AN: 5162

South Asian (SAS) AF: 0.645 AC: 3100 AN: 4806

European-Finnish (FIN) AF: 0.564 AC: 5946 AN: 10536

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35292 AN: 67956

Other (OTH) AF: 0.584 AC: 1234 AN: 2114

Alfa AF: 0.548 Hom.: 64150

Bravo AF: 0.604

Asia WGS AF: 0.753 AC: 2611 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.069
DANN	Benign	0.46
PhyloP100		-2.2
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: rs268972; hg19: chr5-22656527;