rs2446871

Positions:

• chr8-94152281-C-A
• chr8-94152281-C-G
• chr8-94152281-C-T

Variant summary

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

The NM_004063.4(CDH17):​c.1552-169G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,118 control chromosomes in the GnomAD database, including 29,994 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (29994 hom., cov: 33)
• Consequence: CDH17 NM_004063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127

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]

LOC105375647 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH17	NM_004063.4	c.1552-169G>T		intron_variant		ENST00000027335.8	NP_004054.3
LOC105375647	XR_007061012.1	n.518+8008C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH17	ENST00000027335.8	c.1552-169G>T		intron_variant		1	NM_004063.4	ENSP00000027335	P1
CDH17	ENST00000450165.6	c.1552-169G>T		intron_variant		1		ENSP00000401468	P1
CDH17	ENST00000441892.6	c.910-169G>T		intron_variant		2		ENSP00000392811
CDH17	ENST00000520952.1	c.236-3407G>T		intron_variant, NMD_transcript_variant		4		ENSP00000429730

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92165 AN: 152000 Hom.: 29941 Cov.: 33

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.630

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.607 AC: 92289 AN: 152118 Hom.: 29994 Cov.: 33 AF XY: 0.609 AC XY: 45268 AN XY: 74354

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.630

Alfa AF: 0.485 Hom.: 6499

Bravo AF: 0.631

Asia WGS AF: 0.640 AC: 2226 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.9
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2446871; hg19: chr8-95164509;