rs1051624

Variant names:

• chr8-94130944-T-C
• rs1051624
• NM_004063.4:c.2216A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004063.4(CDH17):​c.2216A>G​(p.Glu739Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E739A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDH17 NM_004063.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369
• Publications: 42 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15899205).

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.2216A>G	p.Glu739Gly	missense	Exon 16 of 18	NP_004054.3
	CDH17	NM_001413951.1		c.2273A>G	p.Glu758Gly	missense	Exon 16 of 18	NP_001400880.1
	CDH17	NM_001144663.2		c.2216A>G	p.Glu739Gly	missense	Exon 16 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.2216A>G	p.Glu739Gly	missense	Exon 16 of 18	ENSP00000027335.3	Q12864
	CDH17	ENST00000450165.6	TSL:1	c.2216A>G	p.Glu739Gly	missense	Exon 16 of 18	ENSP00000401468.2	Q12864
	CDH17	ENST00000877574.1		c.2273A>G	p.Glu758Gly	missense	Exon 16 of 18	ENSP00000547633.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1457366 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725378

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107956

Other (OTH) AF: 0.00 AC: 0 AN: 60260

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 92325

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.31	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.37
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.025
Sift	Benign	0.23	T
Sift4G	Benign	0.17	T
Polyphen		0.014	B
Vest4		0.15
MutPred		0.35		Loss of stability (P = 0.0075)
MVP		0.38
MPC		0.080
ClinPred		0.30	T
GERP RS		0.45
Varity_R		0.049
gMVP		0.72
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1051624; hg19: chr8-95143172;