16-61943545-A-G

Variant names:

• chr16-61943545-A-G
• rs3784847
• NM_001796.5:c.253-42072T>C

Variant summary

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

The NM_001796.5(CDH8):​c.253-42072T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0978 in 152,280 control chromosomes in the GnomAD database, including 955 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 0.098 (955 hom., cov: 33)
• Consequence: CDH8 NM_001796.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 5 publications found

Genes affected

CDH8 (HGNC:1767): (cadherin 8) This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. The extracellular domain consists of 5 subdomains, each containing a cadherin motif, and appears to determine the specificity of the protein's homophilic cell adhesion activity. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. This particular cadherin is expressed in brain and is putatively involved in synaptic adhesion, axon outgrowth and guidance. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001796.5. 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
	CDH8	NM_001796.5	MANE Select	c.253-42072T>C		intron	N/A	NP_001787.2
	CDH8	NM_001410893.1		c.253-42072T>C		intron	N/A	NP_001397822.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH8	ENST00000577390.6	TSL:1 MANE Select	c.253-42072T>C		intron	N/A	ENSP00000462701.1
	CDH8	ENST00000299345.10	TSL:5	c.253-42072T>C		intron	N/A	ENSP00000299345.6
	CDH8	ENST00000577730.5	TSL:5	c.253-42072T>C		intron	N/A	ENSP00000462018.1

Frequencies

GnomAD3 genomes AF: 0.0978 AC: 14875 AN: 152162 Hom.: 948 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.0917

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

GnomAD4 genome AF: 0.0978 AC: 14890 AN: 152280 Hom.: 955 Cov.: 33 AF XY: 0.100 AC XY: 7466 AN XY: 74460

African (AFR) AF: 0.111 AC: 4608 AN: 41562

American (AMR) AF: 0.133 AC: 2036 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 507 AN: 3468

East Asian (EAS) AF: 0.285 AC: 1476 AN: 5172

South Asian (SAS) AF: 0.137 AC: 662 AN: 4820

European-Finnish (FIN) AF: 0.0649 AC: 689 AN: 10618

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0673 AC: 4575 AN: 68016

Other (OTH) AF: 0.0893 AC: 189 AN: 2116

Alfa AF: 0.0767 Hom.: 709

Bravo AF: 0.104

Asia WGS AF: 0.210 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.5
DANN	Benign	0.77
PhyloP100		1.0
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: rs3784847; hg19: chr16-61977449;