chr20-61353181-T-C

Position:

• chr20-61353181-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001794.5(CDH4):​c.169+98244T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 152,012 control chromosomes in the GnomAD database, including 20,403 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 0.51 (20403 hom., cov: 32)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH4	NM_001794.5	c.169+98244T>C		intron_variant		ENST00000614565.5	NP_001785.2
CDH4	XM_047439812.1	c.-54+98244T>C		intron_variant			XP_047295768.1
CDH4	XM_047439813.1	c.-54+98244T>C		intron_variant			XP_047295769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH4	ENST00000614565.5	c.169+98244T>C		intron_variant		1	NM_001794.5	ENSP00000484928	P1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77655 AN: 151894 Hom.: 20381 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.511 AC: 77717 AN: 152012 Hom.: 20403 Cov.: 32 AF XY: 0.510 AC XY: 37878 AN XY: 74282

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.531

Alfa AF: 0.568 Hom.: 28052

Bravo AF: 0.504

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.015
DANN	Benign	0.49

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: rs4468878; hg19: chr20-59928237;