8-94176622-T-C

Position:

• chr8-94176622-T-C

Variant summary

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

The NM_004063.4(CDH17):​c.343A>G​(p.Lys115Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 1,613,186 control chromosomes in the GnomAD database, including 499,617 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.81 (50940 hom., cov: 32)
  • Exomes 𝑓: 0.78 (448677 hom.)
• Consequence: CDH17 NM_004063.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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]

CDH17 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6419847E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH17	NM_004063.4	c.343A>G	p.Lys115Glu	missense_variant	5/18	ENST00000027335.8	NP_004054.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH17	ENST00000027335.8	c.343A>G	p.Lys115Glu	missense_variant	5/18	1	NM_004063.4	ENSP00000027335.3
CDH17	ENST00000450165.6	c.343A>G	p.Lys115Glu	missense_variant	5/18	1		ENSP00000401468.2
CDH17	ENST00000441892.6	c.343A>G	p.Lys115Glu	missense_variant	5/13	2		ENSP00000392811.2
CDH17	ENST00000521491.1	c.343A>G	p.Lys115Glu	missense_variant	6/7	5		ENSP00000428189.1

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123780 AN: 151988 Hom.: 50893 Cov.: 32

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.812

GnomAD3 exomes AF: 0.770 AC: 193218 AN: 251064 Hom.: 75032 AF XY: 0.771 AC XY: 104639 AN XY: 135688

Gnomad AFR exome AF: 0.927

Gnomad AMR exome AF: 0.733

Gnomad ASJ exome AF: 0.757

Gnomad EAS exome AF: 0.622

Gnomad SAS exome AF: 0.809

Gnomad FIN exome AF: 0.688

Gnomad NFE exome AF: 0.788

Gnomad OTH exome AF: 0.778

GnomAD4 exome AF: 0.782 AC: 1142997 AN: 1461080 Hom.: 448677 Cov.: 43 AF XY: 0.783 AC XY: 569001 AN XY: 726856

Gnomad4 AFR exome AF: 0.931

Gnomad4 AMR exome AF: 0.739

Gnomad4 ASJ exome AF: 0.752

Gnomad4 EAS exome AF: 0.627

Gnomad4 SAS exome AF: 0.806

Gnomad4 FIN exome AF: 0.702

Gnomad4 NFE exome AF: 0.788

Gnomad4 OTH exome AF: 0.785

GnomAD4 genome AF: 0.814 AC: 123881 AN: 152106 Hom.: 50940 Cov.: 32 AF XY: 0.809 AC XY: 60106 AN XY: 74326

Gnomad4 AFR AF: 0.927

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.816

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.806

Alfa AF: 0.790 Hom.: 79455

Bravo AF: 0.823

TwinsUK AF: 0.774 AC: 2869

ALSPAC AF: 0.791 AC: 3048

ESP6500AA AF: 0.920 AC: 4054

ESP6500EA AF: 0.786 AC: 6759

ExAC AF: 0.775 AC: 94061

EpiCase AF: 0.798

EpiControl AF: 0.797

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.047	T;.;T;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.032	.;T;T;T
MetaRNN	Benign	0.0000016	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.075	N;.;N;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.89	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.45	T;T;T;T
Sift4G	Benign	1.0	T;T;T;.
Polyphen		0.0	B;B;B;.
Vest4		0.088
MPC		0.091
ClinPred		0.0044	T
GERP RS		4.1
Varity_R		0.068
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2243518; hg19: chr8-95188850; COSMIC: COSV50326476;