rs2514805

Variant names:

• chr8-94155019-A-G
• rs2514805
• NM_004063.4:c.1552-2907T>C

Variant summary

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

The NM_004063.4(CDH17):​c.1552-2907T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0975 in 152,098 control chromosomes in the GnomAD database, including 811 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 (811 hom., cov: 31)
• Consequence: CDH17 NM_004063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 7 publications found

Genes affected

CDH17 (HGNC:1756): (cadherin 17) This gene is a member of the cadherin superfamily, genes encoding calcium-dependent, membrane-associated glycoproteins. The encoded protein is cadherin-like, consisting of an extracellular region, containing 7 cadherin domains, and a transmembrane region but lacking the conserved cytoplasmic domain. The protein is a component of the gastrointestinal tract and pancreatic ducts, acting as an intestinal proton-dependent peptide transporter in the first step in oral absorption of many medically important peptide-based drugs. The protein may also play a role in the morphological organization of liver and intestine. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

ENSG00000304524 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH17	NM_004063.4	c.1552-2907T>C		intron_variant	Intron 12 of 17	ENST00000027335.8	NP_004054.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH17	ENST00000027335.8	c.1552-2907T>C		intron_variant	Intron 12 of 17	1	NM_004063.4	ENSP00000027335.3

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14804 AN: 151980 Hom.: 804 Cov.: 31

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0920

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.000775

Gnomad SAS AF: 0.0616

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.0975 AC: 14833 AN: 152098 Hom.: 811 Cov.: 31 AF XY: 0.0972 AC XY: 7229 AN XY: 74344

African (AFR) AF: 0.0729 AC: 3025 AN: 41504

American (AMR) AF: 0.0917 AC: 1403 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3468

East Asian (EAS) AF: 0.000777 AC: 4 AN: 5148

South Asian (SAS) AF: 0.0623 AC: 300 AN: 4816

European-Finnish (FIN) AF: 0.125 AC: 1326 AN: 10580

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7877 AN: 67972

Other (OTH) AF: 0.117 AC: 248 AN: 2112

Alfa AF: 0.106 Hom.: 1661

Bravo AF: 0.0946

Asia WGS AF: 0.0370 AC: 129 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.35
PhyloP100		-0.30
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: rs2514805; hg19: chr8-95167247;