rs7203175

Variant names:

• chr16-83670784-T-C
• rs7203175
• NM_001257.5:c.1102-6T>C

Variant summary

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

The NM_001220488.2(CDH13):​c.1243-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0711 in 1,613,100 control chromosomes in the GnomAD database, including 4,447 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (449 hom., cov: 32)
  • Exomes 𝑓: 0.071 (3998 hom.)
• Consequence: CDH13 NM_001220488.2 splice_region, intron
• Scores: Splicing: ADA: 0.00004345
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.39
• Publications: 8 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]

LOC124900603 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 16-83670784-T-C is Benign according to our data. Variant chr16-83670784-T-C is described in ClinVar as Benign. ClinVar VariationId is 257641.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0919 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001220488.2. 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.1102-6T>C		splice_region intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.1243-6T>C		splice_region intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.985-6T>C		splice_region intron	N/A	NP_001207418.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.1102-6T>C		splice_region intron	N/A	ENSP00000479395.1
	CDH13	ENST00000268613.14	TSL:2	c.1243-6T>C		splice_region intron	N/A	ENSP00000268613.10
	CDH13	ENST00000428848.7	TSL:2	c.985-6T>C		splice_region intron	N/A	ENSP00000394557.3

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 11027 AN: 152136 Hom.: 448 Cov.: 32

Gnomad AFR AF: 0.0944

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.0438

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.00499

Gnomad SAS AF: 0.0875

Gnomad FIN AF: 0.0543

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0695

Gnomad OTH AF: 0.0756

GnomAD2 exomes AF: 0.0662 AC: 16472 AN: 248930 AF XY: 0.0685

Gnomad AFR exome AF: 0.0971

Gnomad AMR exome AF: 0.0328

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.00585

Gnomad FIN exome AF: 0.0618

Gnomad NFE exome AF: 0.0703

Gnomad OTH exome AF: 0.0750

GnomAD4 exome AF: 0.0709 AC: 103614 AN: 1460846 Hom.: 3998 Cov.: 31 AF XY: 0.0718 AC XY: 52202 AN XY: 726744

African (AFR) AF: 0.0944 AC: 3158 AN: 33454

American (AMR) AF: 0.0340 AC: 1518 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 3394 AN: 26120

East Asian (EAS) AF: 0.00398 AC: 158 AN: 39694

South Asian (SAS) AF: 0.0914 AC: 7882 AN: 86228

European-Finnish (FIN) AF: 0.0636 AC: 3394 AN: 53394

Middle Eastern (MID) AF: 0.0847 AC: 488 AN: 5764

European-Non Finnish (NFE) AF: 0.0713 AC: 79198 AN: 1111150

Other (OTH) AF: 0.0733 AC: 4424 AN: 60342

GnomAD4 genome AF: 0.0724 AC: 11029 AN: 152254 Hom.: 449 Cov.: 32 AF XY: 0.0712 AC XY: 5298 AN XY: 74444

African (AFR) AF: 0.0943 AC: 3918 AN: 41532

American (AMR) AF: 0.0435 AC: 666 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3470

East Asian (EAS) AF: 0.00501 AC: 26 AN: 5194

South Asian (SAS) AF: 0.0873 AC: 420 AN: 4810

European-Finnish (FIN) AF: 0.0543 AC: 576 AN: 10606

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0695 AC: 4728 AN: 68032

Other (OTH) AF: 0.0748 AC: 158 AN: 2112

Alfa AF: 0.0756 Hom.: 615

Bravo AF: 0.0709

Asia WGS AF: 0.0400 AC: 141 AN: 3478

EpiCase AF: 0.0745

EpiControl AF: 0.0701

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	10
DANN	Benign	0.64
PhyloP100		1.4
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000043
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs7203175; hg19: chr16-83704389;