8-94212945-A-G

Variant names:

• chr8-94212945-A-G
• rs6989467
• ENST00000450165.6:c.-21+4253T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000450165.6(CDH17):​c.-21+4253T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,086 control chromosomes in the GnomAD database, including 39,496 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 0.71 (39496 hom., cov: 32)
• Consequence: CDH17 ENST00000450165.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 14 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH17	NM_001144663.2	c.-21+4253T>C		intron_variant	Intron 1 of 17		NP_001138135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH17	ENST00000450165.6	c.-21+4253T>C		intron_variant	Intron 1 of 17	1		ENSP00000401468.2

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108205 AN: 151968 Hom.: 39459 Cov.: 32

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.712 AC: 108293 AN: 152086 Hom.: 39496 Cov.: 32 AF XY: 0.702 AC XY: 52181 AN XY: 74340

African (AFR) AF: 0.839 AC: 34795 AN: 41494

American (AMR) AF: 0.608 AC: 9294 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2251 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1692 AN: 5164

South Asian (SAS) AF: 0.614 AC: 2959 AN: 4816

European-Finnish (FIN) AF: 0.606 AC: 6412 AN: 10576

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48480 AN: 67972

Other (OTH) AF: 0.713 AC: 1504 AN: 2110

Alfa AF: 0.705 Hom.: 169667

Bravo AF: 0.715

Asia WGS AF: 0.510 AC: 1778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6989467; hg19: chr8-95225173;