rs12605720

Positions:

• chr18-65833954-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH7	NM_004361.5	c.981+9123A>G		intron_variant		ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.981+9123A>G		intron_variant			NP_001349367.1
CDH7	NM_033646.4	c.981+9123A>G		intron_variant			NP_387450.1
CDH7	NM_001317214.3	c.981+9123A>G		intron_variant			NP_001304143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH7	ENST00000397968.4	c.981+9123A>G		intron_variant		1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.981+9123A>G		intron_variant		1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.981+9123A>G		intron_variant		1		ENSP00000443030.2

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

Gnomad4 AFR AF: 0.00816

Gnomad4 AMR AF: 0.0183

Gnomad4 ASJ AF: 0.0522

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.0572

Gnomad4 FIN AF: 0.0400

Gnomad4 NFE AF: 0.0259

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.0242 Hom.: 10

Bravo AF: 0.0269

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.75

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: rs12605720; hg19: chr18-63501190;