rs780179

Variant names:

• chr5-22812155-T-C
• rs780179
• NM_004061.5:c.-523+40903A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-22812155-T-C
• chr5-22812155-T-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.-523+40903A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,974 control chromosomes in the GnomAD database, including 21,176 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 0.52 (21176 hom., cov: 31)
• Consequence: CDH12 NM_004061.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• Publications: 9 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 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+40903A>G		intron	N/A	NP_004052.2
	CDH12	NM_001364104.2		c.-428+40903A>G		intron	N/A	NP_001351033.1
	CDH12	NM_001364105.2		c.-615-1446A>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.-523+40903A>G		intron	N/A	ENSP00000371689.1
	CDH12	ENST00000504376.6	TSL:5	c.-428+40903A>G		intron	N/A	ENSP00000423577.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79387 AN: 151856 Hom.: 21166 Cov.: 31

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.523 AC: 79447 AN: 151974 Hom.: 21176 Cov.: 31 AF XY: 0.520 AC XY: 38628 AN XY: 74290

African (AFR) AF: 0.613 AC: 25407 AN: 41452

American (AMR) AF: 0.482 AC: 7360 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2102 AN: 3466

East Asian (EAS) AF: 0.346 AC: 1788 AN: 5170

South Asian (SAS) AF: 0.531 AC: 2558 AN: 4818

European-Finnish (FIN) AF: 0.462 AC: 4875 AN: 10560

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33737 AN: 67944

Other (OTH) AF: 0.538 AC: 1133 AN: 2104

Alfa AF: 0.515 Hom.: 43915

Bravo AF: 0.527

Asia WGS AF: 0.476 AC: 1655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.38
PhyloP100		-0.96
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: rs780179; hg19: chr5-22812264;