chr16-83748390-A-C

Variant names:

• chr16-83748390-A-C
• rs3743616
• NM_001257.5:c.1681+140A>C

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.1681+140A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 720,782 control chromosomes in the GnomAD database, including 750 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (126 hom., cov: 32)
  • Exomes 𝑓: 0.041 (624 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0290
• 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]

CEDORA (HGNC:56653): (CDH13 antisense oligodendrocyte and neuron associated lncRNA)

HSBP1 (HGNC:5203): (heat shock factor binding protein 1) The heat-shock response is elicited by exposure of cells to thermal and chemical stress and through the activation of HSFs (heat shock factors) results in the elevated expression of heat-shock induced genes. Heat shock factor binding protein 1 (HSBP1), is a 76-amino-acid protein that binds to heat shock factor 1(HSF1), which is a transcription factor involved in the HS response. During HS response, HSF1 undergoes conformational transition from an inert non-DNA-binding monomer to active functional trimers. HSBP1 is nuclear-localized and interacts with the active trimeric state of HSF1 to negatively regulate HSF1 DNA-binding activity. Overexpression of HSBP1 in mammalian cells represses the transactivation activity of HSF1. When overexpressed in C.elegans HSBP1 has severe effects on survival of the animals after thermal and chemical stress consistent with a role of HSBP1 as a negative regulator of heat shock response. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-83748390-A-C is Benign according to our data. Variant chr16-83748390-A-C is described in ClinVar as Benign. ClinVar VariationId is 1285859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.079 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.1681+140A>C		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.1822+140A>C		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.1564+140A>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.1681+140A>C		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000268613.14	TSL:2	c.1822+140A>C		intron	N/A	ENSP00000268613.10	P55290-4
	CDH13	ENST00000428848.7	TSL:2	c.1564+140A>C		intron	N/A	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes AF: 0.0332 AC: 5053 AN: 152216 Hom.: 126 Cov.: 32

Gnomad AFR AF: 0.00764

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0341

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0854

Gnomad SAS AF: 0.0161

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0413

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.0411 AC: 23360 AN: 568448 Hom.: 624 AF XY: 0.0402 AC XY: 11867 AN XY: 295136

African (AFR) AF: 0.00722 AC: 113 AN: 15654

American (AMR) AF: 0.0361 AC: 839 AN: 23226

Ashkenazi Jewish (ASJ) AF: 0.0128 AC: 181 AN: 14110

East Asian (EAS) AF: 0.100 AC: 3431 AN: 34166

South Asian (SAS) AF: 0.0167 AC: 676 AN: 40582

European-Finnish (FIN) AF: 0.0644 AC: 2170 AN: 33680

Middle Eastern (MID) AF: 0.0266 AC: 71 AN: 2670

European-Non Finnish (NFE) AF: 0.0395 AC: 14791 AN: 374588

Other (OTH) AF: 0.0365 AC: 1088 AN: 29772

GnomAD4 genome AF: 0.0332 AC: 5051 AN: 152334 Hom.: 126 Cov.: 32 AF XY: 0.0346 AC XY: 2575 AN XY: 74488

African (AFR) AF: 0.00762 AC: 317 AN: 41588

American (AMR) AF: 0.0342 AC: 523 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.0856 AC: 443 AN: 5176

South Asian (SAS) AF: 0.0157 AC: 76 AN: 4828

European-Finnish (FIN) AF: 0.0651 AC: 691 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0413 AC: 2806 AN: 68022

Other (OTH) AF: 0.0284 AC: 60 AN: 2116

Alfa AF: 0.0369 Hom.: 14

Bravo AF: 0.0299

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.83
CADD	Benign	0.53
DANN	Benign	0.67
PhyloP100		-0.029
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: rs3743616; hg19: chr16-83781995; COSMIC: COSV51809761;