rs16985493

chr20-61718507-G-Achr20-61718507-G-T

Variant summary

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

The NM_001794.5(CDH4):c.170-25056G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 317,434 control chromosomes in the GnomAD database, including 442 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 0.053 (256 hom., cov: 34)
  • Exomes 𝑓: 0.039 (186 hom.)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH4	NM_001794.5	c.170-25056G>A		intron_variant		ENST00000614565.5
LOC100128310	NR_147702.1	n.999C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH4	ENST00000614565.5	c.170-25056G>A		intron_variant		1	NM_001794.5	P1
	ENST00000317652.1	n.999C>T		non_coding_transcript_exon_variant	2/2	2
CDH4	ENST00000543233.2	c.-53-25056G>A		intron_variant		2
CDH4	ENST00000611855.4	c.50-25056G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0530 AC: 8069 AN: 152184 Hom.: 254 Cov.: 34

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00704

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.0593

GnomAD4 exome AF: 0.0387 AC: 6386 AN: 165132 Hom.: 186 Cov.: 0 AF XY: 0.0352 AC XY: 3112 AN XY: 88408

Gnomad4 AFR exome AF: 0.0818

Gnomad4 AMR exome AF: 0.0381

Gnomad4 ASJ exome AF: 0.0687

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00599

Gnomad4 FIN exome AF: 0.0211

Gnomad4 NFE exome AF: 0.0494

Gnomad4 OTH exome AF: 0.0473

GnomAD4 genome AF: 0.0530 AC: 8068 AN: 152302 Hom.: 256 Cov.: 34 AF XY: 0.0496 AC XY: 3692 AN XY: 74478

Gnomad4 AFR AF: 0.0752

Gnomad4 AMR AF: 0.0465

Gnomad4 ASJ AF: 0.0700

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.0182

Gnomad4 NFE AF: 0.0529

Gnomad4 OTH AF: 0.0587

Alfa AF: 0.0486 Hom.: 217

Bravo AF: 0.0558

Asia WGS AF: 0.00866 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.0
Dann	Benign	0.65

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: rs16985493; hg19: chr20-60293563;