NM_004361.5:c.210+4972C>T

Variant names:

• chr18-65768024-C-T
• rs7237421
• NM_004361.5:c.210+4972C>T

Variant summary

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

The NM_004361.5(CDH7):​c.210+4972C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,994 control chromosomes in the GnomAD database, including 17,695 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 0.44 (17695 hom., cov: 32)
• Consequence: CDH7 NM_004361.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH7	NM_004361.5	MANE Select	c.210+4972C>T		intron	N/A	NP_004352.2
	CDH7	NM_001362438.2		c.210+4972C>T		intron	N/A	NP_001349367.1
	CDH7	NM_033646.4		c.210+4972C>T		intron	N/A	NP_387450.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH7	ENST00000397968.4	TSL:1 MANE Select	c.210+4972C>T		intron	N/A	ENSP00000381058.2
	CDH7	ENST00000323011.7	TSL:1	c.210+4972C>T		intron	N/A	ENSP00000319166.3
	CDH7	ENST00000536984.6	TSL:1	c.210+4972C>T		intron	N/A	ENSP00000443030.2

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67098 AN: 151876 Hom.: 17646 Cov.: 32

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.442 AC: 67192 AN: 151994 Hom.: 17695 Cov.: 32 AF XY: 0.445 AC XY: 33040 AN XY: 74290

African (AFR) AF: 0.745 AC: 30896 AN: 41470

American (AMR) AF: 0.319 AC: 4880 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3472

East Asian (EAS) AF: 0.345 AC: 1777 AN: 5144

South Asian (SAS) AF: 0.442 AC: 2134 AN: 4824

European-Finnish (FIN) AF: 0.412 AC: 4339 AN: 10542

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.307 AC: 20868 AN: 67952

Other (OTH) AF: 0.386 AC: 817 AN: 2114

Alfa AF: 0.345 Hom.: 12736

Bravo AF: 0.444

Asia WGS AF: 0.459 AC: 1596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.1
DANN	Benign	0.42
PhyloP100		1.6
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: rs7237421; hg19: chr18-63435260;