NM_001257.5:c.158-124G>C

Variant names:

• chr16-83031886-G-C
• rs7189859
• NM_001257.5:c.158-124G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001257.5(CDH13):​c.158-124G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 742,346 control chromosomes in the GnomAD database, including 4,387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1144 hom., cov: 32)
  • Exomes 𝑓: 0.10 (3243 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-83031886-G-C is Benign according to our data. Variant chr16-83031886-G-C is described in ClinVar as Benign. ClinVar VariationId is 1239670.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 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.158-124G>C		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.299-124G>C		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.158-124G>C		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.158-124G>C		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000431540.7	TSL:1	c.158-124G>C		intron	N/A	ENSP00000408632.3	P55290-2
	CDH13	ENST00000268613.14	TSL:2	c.299-124G>C		intron	N/A	ENSP00000268613.10	P55290-4

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17845 AN: 152040 Hom.: 1143 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0521

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.102 AC: 60032 AN: 590188 Hom.: 3243 AF XY: 0.102 AC XY: 31150 AN XY: 305412

African (AFR) AF: 0.168 AC: 2639 AN: 15696

American (AMR) AF: 0.0661 AC: 1755 AN: 26536

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 1824 AN: 15836

East Asian (EAS) AF: 0.0726 AC: 2303 AN: 31720

South Asian (SAS) AF: 0.103 AC: 5256 AN: 50788

European-Finnish (FIN) AF: 0.117 AC: 4670 AN: 39762

Middle Eastern (MID) AF: 0.0887 AC: 208 AN: 2346

European-Non Finnish (NFE) AF: 0.101 AC: 38193 AN: 376892

Other (OTH) AF: 0.104 AC: 3184 AN: 30612

GnomAD4 genome AF: 0.117 AC: 17857 AN: 152158 Hom.: 1144 Cov.: 32 AF XY: 0.115 AC XY: 8589 AN XY: 74414

African (AFR) AF: 0.167 AC: 6938 AN: 41502

American (AMR) AF: 0.0784 AC: 1198 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 395 AN: 3470

East Asian (EAS) AF: 0.0526 AC: 272 AN: 5170

South Asian (SAS) AF: 0.107 AC: 516 AN: 4820

European-Finnish (FIN) AF: 0.116 AC: 1233 AN: 10602

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6905 AN: 68004

Other (OTH) AF: 0.110 AC: 231 AN: 2106

Alfa AF: 0.0376 Hom.: 40

Bravo AF: 0.116

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.21
DANN	Benign	0.39
PhyloP100		-1.1
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: rs7189859; hg19: chr16-83065491;