NM_001257.5:c.45+12305C>T

Variant names:

• chr16-82639442-C-T
• rs4782724
• NM_001257.5:c.45+12305C>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.45+12305C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,535,282 control chromosomes in the GnomAD database, including 753,368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68789 hom., cov: 32)
  • Exomes 𝑓: 0.99 (684579 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.187
• Publications: 18 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 (MetaRNN=1.2290827E-6).
• BP6: Variant 16-82639442-C-T is Benign according to our data. Variant chr16-82639442-C-T is described in ClinVar as Benign. ClinVar VariationId is 257644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.45+12305C>T		intron_variant	Intron 1 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.45+12305C>T		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.947 AC: 144095 AN: 152146 Hom.: 68735 Cov.: 32

Gnomad AFR AF: 0.818

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.956

GnomAD2 exomes AF: 0.989 AC: 126958 AN: 128384 AF XY: 0.991

Gnomad AFR exome AF: 0.823

Gnomad AMR exome AF: 0.990

Gnomad ASJ exome AF: 0.996

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.993

GnomAD4 exome AF: 0.995 AC: 1375544 AN: 1383018 Hom.: 684579 Cov.: 35 AF XY: 0.995 AC XY: 679149 AN XY: 682434

African (AFR) AF: 0.819 AC: 25836 AN: 31556

American (AMR) AF: 0.989 AC: 35287 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 25075 AN: 25176

East Asian (EAS) AF: 1.00 AC: 35730 AN: 35730

South Asian (SAS) AF: 1.00 AC: 79195 AN: 79232

European-Finnish (FIN) AF: 1.00 AC: 33468 AN: 33468

Middle Eastern (MID) AF: 0.990 AC: 5637 AN: 5694

European-Non Finnish (NFE) AF: 1.00 AC: 1078148 AN: 1078580

Other (OTH) AF: 0.988 AC: 57168 AN: 57886

GnomAD4 genome AF: 0.947 AC: 144209 AN: 152264 Hom.: 68789 Cov.: 32 AF XY: 0.949 AC XY: 70650 AN XY: 74444

African (AFR) AF: 0.819 AC: 33999 AN: 41522

American (AMR) AF: 0.976 AC: 14938 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3461 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5174

South Asian (SAS) AF: 1.00 AC: 4814 AN: 4814

European-Finnish (FIN) AF: 1.00 AC: 10612 AN: 10612

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67988 AN: 68044

Other (OTH) AF: 0.956 AC: 2022 AN: 2114

Alfa AF: 0.983 Hom.: 121946

Bravo AF: 0.938

TwinsUK AF: 1.00 AC: 3707

ALSPAC AF: 1.00 AC: 3853

ExAC AF: 0.982 AC: 13630

Asia WGS AF: 0.992 AC: 3452 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.8
DANN	Benign	0.37
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.00081	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.19
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.022
Sift	Benign	0.95	T
Vest4		0.017
MPC		0.073
ClinPred		0.0027	T
GERP RS		2.2
gMVP		0.077
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs4782724; hg19: chr16-82673047; COSMIC: COSV107273688;