rs12605720

Variant names:

• chr18-65833954-A-G
• rs12605720
• NM_004361.5:c.981+9123A>G

Variant summary

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

The NM_004361.5(CDH7):​c.981+9123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 152,246 control chromosomes in the GnomAD database, including 134 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 0.028 (134 hom., cov: 32)
• Consequence: CDH7 NM_004361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• Publications: 1 publications found

Genes affected

CDH7 (HGNC:1766): (cadherin 7) This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium dependent cell-cell adhesion molecule is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. 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. Cadherins mediate cell-cell binding in a homophilic manner, contributing to the sorting of heterogeneous cell types. Mutations in this gene may be associated with bipolar disease in human patients. This gene is present in a gene cluster on chromosome 18. [provided by RefSeq, May 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004361.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH7	NM_004361.5	MANE Select	c.981+9123A>G		intron	N/A	NP_004352.2
	CDH7	NM_001362438.2		c.981+9123A>G		intron	N/A	NP_001349367.1	Q9ULB5
	CDH7	NM_033646.4		c.981+9123A>G		intron	N/A	NP_387450.1	Q9ULB5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH7	ENST00000397968.4	TSL:1 MANE Select	c.981+9123A>G		intron	N/A	ENSP00000381058.2	Q9ULB5
	CDH7	ENST00000323011.7	TSL:1	c.981+9123A>G		intron	N/A	ENSP00000319166.3	Q9ULB5
	CDH7	ENST00000536984.6	TSL:1	c.981+9123A>G		intron	N/A	ENSP00000443030.2	F5H5X9

Frequencies

GnomAD3 genomes AF: 0.0284 AC: 4313 AN: 152128 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.00821

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0183

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.0400

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0283 AC: 4311 AN: 152246 Hom.: 134 Cov.: 32 AF XY: 0.0311 AC XY: 2311 AN XY: 74420

African (AFR) AF: 0.00816 AC: 339 AN: 41552

American (AMR) AF: 0.0183 AC: 280 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 181 AN: 3470

East Asian (EAS) AF: 0.189 AC: 972 AN: 5150

South Asian (SAS) AF: 0.0572 AC: 276 AN: 4826

European-Finnish (FIN) AF: 0.0400 AC: 425 AN: 10612

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0259 AC: 1759 AN: 68024

Other (OTH) AF: 0.0255 AC: 54 AN: 2114

Alfa AF: 0.0235 Hom.: 19

Bravo AF: 0.0269

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.75
PhyloP100		0.29
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: rs12605720; hg19: chr18-63501190;