rs1051624

Positions:

• chr8-94130944-T-A
• chr8-94130944-T-C
• chr8-94130944-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004063.4(CDH17):​c.2216A>T​(p.Glu739Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,609,072 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E739A) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: CDH17 NM_004063.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07026374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH17	NM_004063.4	c.2216A>T	p.Glu739Val	missense_variant	16/18	ENST00000027335.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH17	ENST00000027335.8	c.2216A>T	p.Glu739Val	missense_variant	16/18	1	NM_004063.4	P1
CDH17	ENST00000450165.6	c.2216A>T	p.Glu739Val	missense_variant	16/18	1		P1
CDH17	ENST00000441892.6	c.1574A>T	p.Glu525Val	missense_variant	12/13	2

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151706 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000727

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000200 AC: 5 AN: 250280 Hom.: 0 AF XY: 0.0000222 AC XY: 3 AN XY: 135206

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1457366 Hom.: 0 Cov.: 33 AF XY: 0.0000221 AC XY: 16 AN XY: 725378

Gnomad4 AFR exome AF: 0.000389

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000903

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151706 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74000

Gnomad4 AFR AF: 0.0000727

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00000312 Hom.: 48131

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.41
DANN	Benign	0.16
DEOGEN2	Benign	0.056	T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0030	N
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.070	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N;.;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.74	N;N;N
REVEL	Benign	0.020
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.11
MutPred		0.40		Loss of disorder (P = 0.037);.;Loss of disorder (P = 0.037);
MVP		0.28
MPC		0.077
ClinPred		0.0086	T
GERP RS		0.45
Varity_R		0.053
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1051624; hg19: chr8-95143172;