8-94130660-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_004063.4(CDH17):c.2364A>G(p.Ala788=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000477 in 1,613,702 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: CDH17 NM_004063.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.206

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 Benign. Variant got -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 8-94130660-T-C is Benign according to our data. Variant chr8-94130660-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 720737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.206 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH17	NM_004063.4	c.2364A>G	p.Ala788=	synonymous_variant	17/18	ENST00000027335.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH17	ENST00000027335.8	c.2364A>G	p.Ala788=	synonymous_variant	17/18	1	NM_004063.4	P1
CDH17	ENST00000450165.6	c.2364A>G	p.Ala788=	synonymous_variant	17/18	1		P1
CDH17	ENST00000441892.6	c.1642+216A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00258 AC: 393 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00897

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

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: 0.00382

GnomAD3 exomes AF: 0.000666 AC: 167 AN: 250836 Hom.: 1 AF XY: 0.000465 AC XY: 63 AN XY: 135530

Gnomad AFR exome AF: 0.00919

Gnomad AMR exome AF: 0.000436

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000259 AC: 378 AN: 1461394 Hom.: 1 Cov.: 30 AF XY: 0.000235 AC XY: 171 AN XY: 726960

Gnomad4 AFR exome AF: 0.00956

Gnomad4 AMR exome AF: 0.000538

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.000497

GnomAD4 genome AF: 0.00257 AC: 392 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.00250 AC XY: 186 AN XY: 74478

Gnomad4 AFR AF: 0.00892

Gnomad4 AMR AF: 0.000850

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: 0.00378

Alfa AF: 0.00119 Hom.: 1

Bravo AF: 0.00300

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2022	CDH17: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	0.36
Dann	Benign	0.49

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: rs146691258; hg19: chr8-95142888;