chr18-65762670-C-T

Variant names:

• chr18-65762670-C-T
• rs7244243
• NM_004361.5:c.-173C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_004361.5(CDH7):​c.-173C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 583,232 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000053 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: CDH7 NM_004361.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 8 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BS2: High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.-173C>T		5_prime_UTR_variant	Exon 2 of 12	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.-173C>T		5_prime_UTR_variant	Exon 2 of 12		NP_001349367.1
CDH7	NM_033646.4	c.-173C>T		5_prime_UTR_variant	Exon 2 of 12		NP_387450.1
CDH7	NM_001317214.3	c.-173C>T		5_prime_UTR_variant	Exon 2 of 11		NP_001304143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH7	ENST00000397968.4	c.-173C>T		5_prime_UTR_variant	Exon 2 of 12	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.-173C>T		5_prime_UTR_variant	Exon 2 of 12	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.-173C>T		5_prime_UTR_variant	Exon 2 of 11	1		ENSP00000443030.2

Frequencies

GnomAD3 genomes AF: 0.0000527 AC: 8 AN: 151738 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000969

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000139 AC: 6 AN: 431494 Hom.: 0 Cov.: 4 AF XY: 0.0000220 AC XY: 5 AN XY: 226810

African (AFR) AF: 0.00 AC: 0 AN: 12066

American (AMR) AF: 0.0000550 AC: 1 AN: 18186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13094

East Asian (EAS) AF: 0.00 AC: 0 AN: 30334

South Asian (SAS) AF: 0.00 AC: 0 AN: 40692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1872

European-Non Finnish (NFE) AF: 0.0000153 AC: 4 AN: 261818

Other (OTH) AF: 0.0000398 AC: 1 AN: 25116

GnomAD4 genome AF: 0.0000527 AC: 8 AN: 151738 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74082

African (AFR) AF: 0.0000969 AC: 4 AN: 41280

American (AMR) AF: 0.0000657 AC: 1 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67960

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 7617

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7244243; hg19: chr18-63429906;