5-21848263-G-T

Variant names:

• chr5-21848263-G-T
• rs7725275
• NM_004061.5:c.647-5935C>A

Variant summary

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

The ENST00000382254.6(CDH12):​c.647-5935C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 151,886 control chromosomes in the GnomAD database, including 35,606 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 0.65 (35606 hom., cov: 33)
• Consequence: CDH12 ENST00000382254.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 0 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000382254.6. 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.647-5935C>A		intron	N/A	NP_004052.2
	CDH12	NM_001317227.2		c.647-5935C>A		intron	N/A	NP_001304156.1
	CDH12	NM_001364104.2		c.647-5935C>A		intron	N/A	NP_001351033.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH12	ENST00000382254.6	TSL:1 MANE Select	c.647-5935C>A		intron	N/A	ENSP00000371689.1
	CDH12	ENST00000517378.1	TSL:1	n.1105-5935C>A		intron	N/A
	CDH12	ENST00000504376.6	TSL:5	c.647-5935C>A		intron	N/A	ENSP00000423577.1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99147 AN: 151768 Hom.: 35611 Cov.: 33

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.653 AC: 99154 AN: 151886 Hom.: 35606 Cov.: 33 AF XY: 0.659 AC XY: 48883 AN XY: 74222

African (AFR) AF: 0.326 AC: 13510 AN: 41422

American (AMR) AF: 0.717 AC: 10919 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2942 AN: 3468

East Asian (EAS) AF: 0.796 AC: 4089 AN: 5138

South Asian (SAS) AF: 0.683 AC: 3294 AN: 4824

European-Finnish (FIN) AF: 0.817 AC: 8632 AN: 10570

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.786 AC: 53376 AN: 67926

Other (OTH) AF: 0.681 AC: 1437 AN: 2110

Alfa AF: 0.713 Hom.: 9260

Bravo AF: 0.630

Asia WGS AF: 0.712 AC: 2467 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.10
PhyloP100		0.11
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: rs7725275; hg19: chr5-21848372;