20-61852870-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001794.5(CDH4):c.849C>T(p.Asn283=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 in 1,613,958 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0055 (29 hom.)
• Consequence: CDH4 NM_001794.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00500

Genes affected

CDH4 (HGNC:1763): (cadherin 4) This gene is a classical cadherin from the cadherin superfamily. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Based on studies in chicken and mouse, this cadherin is thought to play an important role during brain segmentation and neuronal outgrowth. In addition, a role in kidney and muscle development is indicated. Of particular interest are studies showing stable cis-heterodimers of cadherins 2 and 4 in cotransfected cell lines. Previously thought to interact in an exclusively homophilic manner, this is the first evidence of cadherin heterodimerization. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 20-61852870-C-T is Benign according to our data. Variant chr20-61852870-C-T is described in ClinVar as [Benign]. Clinvar id is 771937.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.005 with no splicing effect.
• BS2: High AC in GnomAd at 697 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH4	NM_001794.5	c.849C>T	p.Asn283=	synonymous_variant	6/16	ENST00000614565.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH4	ENST00000614565.5	c.849C>T	p.Asn283=	synonymous_variant	6/16	1	NM_001794.5	P1
CDH4	ENST00000543233.2	c.627C>T	p.Asn209=	synonymous_variant	5/15	2
CDH4	ENST00000611855.4	c.567C>T	p.Asn189=	synonymous_variant	5/15	5

Frequencies

GnomAD3 genomes AF: 0.00458 AC: 697 AN: 152248 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00335

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00711

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00416 AC: 1045 AN: 251192 Hom.: 3 AF XY: 0.00418 AC XY: 567 AN XY: 135768

Gnomad AFR exome AF: 0.00314

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00497

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000817

Gnomad FIN exome AF: 0.00166

Gnomad NFE exome AF: 0.00714

Gnomad OTH exome AF: 0.00408

GnomAD4 exome AF: 0.00552 AC: 8064 AN: 1461594 Hom.: 29 Cov.: 31 AF XY: 0.00542 AC XY: 3938 AN XY: 727100

Gnomad4 AFR exome AF: 0.00278

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00559

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.000951

Gnomad4 FIN exome AF: 0.00159

Gnomad4 NFE exome AF: 0.00661

Gnomad4 OTH exome AF: 0.00353

GnomAD4 genome AF: 0.00457 AC: 697 AN: 152364 Hom.: 4 Cov.: 33 AF XY: 0.00415 AC XY: 309 AN XY: 74520

Gnomad4 AFR AF: 0.00334

Gnomad4 AMR AF: 0.00287

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00711

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00667 Hom.: 1

Bravo AF: 0.00467

EpiCase AF: 0.00649

EpiControl AF: 0.00599

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	8.5
Dann	Benign	0.79

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: rs139703524; hg19: chr20-60427926; COSMIC: COSV64641619;