rs17740895

Variant names:

• chr16-82858291-G-A
• rs17740895
• NM_001257.5:c.46-71G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-82858291-G-A
• chr16-82858291-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001257.5(CDH13):​c.46-71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 962,458 control chromosomes in the GnomAD database, including 6,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1000 hom., cov: 33)
  • Exomes 𝑓: 0.11 (5622 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.285
• Publications: 4 publications found

Genes affected

CDH13 (HGNC:1753): (cadherin 13) This gene encodes a member of the cadherin superfamily. The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety, rather than by a transmembrane domain. The protein lacks the cytoplasmic domain characteristic of other cadherins, and so is not thought to be a cell-cell adhesion glycoprotein. This protein acts as a negative regulator of axon growth during neural differentiation. It also protects vascular endothelial cells from apoptosis due to oxidative stress, and is associated with resistance to atherosclerosis. The gene is hypermethylated in many types of cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 16-82858291-G-A is Benign according to our data. Variant chr16-82858291-G-A is described in ClinVar as Benign. ClinVar VariationId is 1241506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257.5. 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
	CDH13	NM_001257.5	MANE Select	c.46-71G>A		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.187-71G>A		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.46-71G>A		intron	N/A	NP_001207418.1	P55290-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.46-71G>A		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000431540.7	TSL:1	c.46-71G>A		intron	N/A	ENSP00000408632.3	P55290-2
	CDH13	ENST00000567445.1	TSL:1	c.46-71G>A		intron	N/A	ENSP00000456297.1	H3BRL7

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17144 AN: 152054 Hom.: 993 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.0565

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.111 AC: 90174 AN: 810286 Hom.: 5622 AF XY: 0.111 AC XY: 46545 AN XY: 417518

African (AFR) AF: 0.105 AC: 2080 AN: 19856

American (AMR) AF: 0.234 AC: 7966 AN: 34050

Ashkenazi Jewish (ASJ) AF: 0.0729 AC: 1423 AN: 19522

East Asian (EAS) AF: 0.0573 AC: 2026 AN: 35332

South Asian (SAS) AF: 0.137 AC: 8512 AN: 62206

European-Finnish (FIN) AF: 0.122 AC: 6132 AN: 50382

Middle Eastern (MID) AF: 0.0664 AC: 285 AN: 4292

European-Non Finnish (NFE) AF: 0.106 AC: 57773 AN: 546282

Other (OTH) AF: 0.104 AC: 3977 AN: 38364

GnomAD4 genome AF: 0.113 AC: 17168 AN: 152172 Hom.: 1000 Cov.: 33 AF XY: 0.115 AC XY: 8585 AN XY: 74404

African (AFR) AF: 0.108 AC: 4463 AN: 41506

American (AMR) AF: 0.177 AC: 2698 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0752 AC: 261 AN: 3472

East Asian (EAS) AF: 0.0564 AC: 291 AN: 5160

South Asian (SAS) AF: 0.143 AC: 691 AN: 4828

European-Finnish (FIN) AF: 0.119 AC: 1265 AN: 10586

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7200 AN: 68016

Other (OTH) AF: 0.106 AC: 225 AN: 2114

Alfa AF: 0.110 Hom.: 488

Bravo AF: 0.116

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.4
DANN	Benign	0.73
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17740895; hg19: chr16-82891896;