rs7194373

Variant names:

• chr16-82639485-T-G
• rs7194373
• NM_001257.5:c.45+12348T>G

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.45+12348T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 1,476,718 control chromosomes in the GnomAD database, including 377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (202 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (175 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.569
• Publications: 0 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=-0.87).
• BP6: Variant 16-82639485-T-G is Benign according to our data. Variant chr16-82639485-T-G is described in ClinVar as Benign. ClinVar VariationId is 257646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0928 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.45+12348T>G		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.186+20T>G		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.45+12348T>G		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.45+12348T>G		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000431540.7	TSL:1	c.45+12348T>G		intron	N/A	ENSP00000408632.3	P55290-2
	CDH13	ENST00000567445.1	TSL:1	c.45+12348T>G		intron	N/A	ENSP00000456297.1	H3BRL7

Frequencies

GnomAD3 genomes AF: 0.0278 AC: 4234 AN: 152196 Hom.: 201 Cov.: 33

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0181

GnomAD2 exomes AF: 0.00613 AC: 787 AN: 128330 AF XY: 0.00498

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.00563

Gnomad ASJ exome AF: 0.00148

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000378

Gnomad OTH exome AF: 0.00175

GnomAD4 exome AF: 0.00305 AC: 4045 AN: 1324404 Hom.: 175 Cov.: 21 AF XY: 0.00270 AC XY: 1771 AN XY: 656870

African (AFR) AF: 0.100 AC: 3063 AN: 30614

American (AMR) AF: 0.00660 AC: 235 AN: 35622

Ashkenazi Jewish (ASJ) AF: 0.00133 AC: 33 AN: 24792

East Asian (EAS) AF: 0.00 AC: 0 AN: 35432

South Asian (SAS) AF: 0.000295 AC: 23 AN: 78026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33432

Middle Eastern (MID) AF: 0.00501 AC: 28 AN: 5592

European-Non Finnish (NFE) AF: 0.000201 AC: 206 AN: 1025014

Other (OTH) AF: 0.00818 AC: 457 AN: 55880

GnomAD4 genome AF: 0.0279 AC: 4249 AN: 152314 Hom.: 202 Cov.: 33 AF XY: 0.0268 AC XY: 1995 AN XY: 74480

African (AFR) AF: 0.0953 AC: 3959 AN: 41556

American (AMR) AF: 0.0136 AC: 208 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68030

Other (OTH) AF: 0.0180 AC: 38 AN: 2116

Alfa AF: 0.0124 Hom.: 12

Bravo AF: 0.0321

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.47
DANN	Benign	0.54
PhyloP100		-0.57
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: rs7194373; hg19: chr16-82673090;