8-94176622-T-C

Variant names:

• chr8-94176622-T-C
• rs2243518
• NM_004063.4:c.343A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 35 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 (MetaRNN=1.6419847E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004063.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH17	NM_004063.4	MANE Select	c.343A>G	p.Lys115Glu	missense	Exon 5 of 18	NP_004054.3
	CDH17	NM_001413951.1		c.343A>G	p.Lys115Glu	missense	Exon 5 of 18	NP_001400880.1
	CDH17	NM_001144663.2		c.343A>G	p.Lys115Glu	missense	Exon 5 of 18	NP_001138135.1	Q12864

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH17	ENST00000027335.8	TSL:1 MANE Select	c.343A>G	p.Lys115Glu	missense	Exon 5 of 18	ENSP00000027335.3	Q12864
	CDH17	ENST00000450165.6	TSL:1	c.343A>G	p.Lys115Glu	missense	Exon 5 of 18	ENSP00000401468.2	Q12864
	CDH17	ENST00000877574.1		c.343A>G	p.Lys115Glu	missense	Exon 5 of 18	ENSP00000547633.1

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

GnomAD2 exomes AF: 0.770 AC: 193218 AN: 251064 AF XY: 0.771

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 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

African (AFR) AF: 0.931 AC: 31132 AN: 33450

American (AMR) AF: 0.739 AC: 33011 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 19628 AN: 26114

East Asian (EAS) AF: 0.627 AC: 24868 AN: 39652

South Asian (SAS) AF: 0.806 AC: 69522 AN: 86236

European-Finnish (FIN) AF: 0.702 AC: 37471 AN: 53404

Middle Eastern (MID) AF: 0.816 AC: 4701 AN: 5762

European-Non Finnish (NFE) AF: 0.788 AC: 875301 AN: 1111410

Other (OTH) AF: 0.785 AC: 47363 AN: 60360

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

African (AFR) AF: 0.927 AC: 38497 AN: 41542

American (AMR) AF: 0.784 AC: 11968 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2619 AN: 3470

East Asian (EAS) AF: 0.618 AC: 3186 AN: 5152

South Asian (SAS) AF: 0.816 AC: 3931 AN: 4820

European-Finnish (FIN) AF: 0.682 AC: 7191 AN: 10544

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53788 AN: 67988

Other (OTH) AF: 0.806 AC: 1701 AN: 2110

Alfa AF: 0.797 Hom.: 110017

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 v4.9

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
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.032	T
MetaRNN	Benign	0.0000016	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.075	N
PhyloP100		0.13
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.89	N
REVEL	Benign	0.14
Sift	Benign	0.45	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.088
MPC		0.091
ClinPred		0.0044	T
GERP RS		4.1
Varity_R		0.068
gMVP		0.41
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2243518; hg19: chr8-95188850; COSMIC: COSV50326476;