rs72804764

Variant names:

• chr16-83795311-A-G
• rs72804764
• NM_001257.5:c.*281A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-83795311-A-G
• chr16-83795311-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001257.5(CDH13):​c.*281A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 442,404 control chromosomes in the GnomAD database, including 288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (94 hom., cov: 32)
  • Exomes 𝑓: 0.031 (194 hom.)
• Consequence: CDH13 NM_001257.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.88
• Publications: 2 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]

CDH13-AS2 (HGNC:56243): (CDH13 antisense RNA 2)

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=-0.47).
• BP6: Variant 16-83795311-A-G is Benign according to our data. Variant chr16-83795311-A-G is described in ClinVar as Benign. ClinVar VariationId is 1221196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0275 (4184/152282) while in subpopulation NFE AF = 0.0389 (2648/68028). AF 95% confidence interval is 0.0377. There are 94 homozygotes in GnomAd4. There are 2078 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 94 gene

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.*281A>G		3_prime_UTR	Exon 14 of 14	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.*281A>G		3_prime_UTR	Exon 15 of 15	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.*281A>G		3_prime_UTR	Exon 13 of 13	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.*281A>G		3_prime_UTR	Exon 14 of 14	ENSP00000479395.1	P55290-1
	CDH13	ENST00000268613.14	TSL:2	c.*281A>G		3_prime_UTR	Exon 15 of 15	ENSP00000268613.10	P55290-4
	CDH13-AS2	ENST00000561599.2	TSL:4	n.2901T>C		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.0275 AC: 4183 AN: 152164 Hom.: 94 Cov.: 32

Gnomad AFR AF: 0.00707

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0241

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.0308 AC: 8938 AN: 290122 Hom.: 194 Cov.: 0 AF XY: 0.0298 AC XY: 4573 AN XY: 153246

African (AFR) AF: 0.00760 AC: 67 AN: 8816

American (AMR) AF: 0.0202 AC: 220 AN: 10878

Ashkenazi Jewish (ASJ) AF: 0.00740 AC: 66 AN: 8920

East Asian (EAS) AF: 0.000105 AC: 2 AN: 18968

South Asian (SAS) AF: 0.0129 AC: 388 AN: 30188

European-Finnish (FIN) AF: 0.0609 AC: 1001 AN: 16438

Middle Eastern (MID) AF: 0.0186 AC: 27 AN: 1448

European-Non Finnish (NFE) AF: 0.0376 AC: 6671 AN: 177622

Other (OTH) AF: 0.0294 AC: 496 AN: 16844

GnomAD4 genome AF: 0.0275 AC: 4184 AN: 152282 Hom.: 94 Cov.: 32 AF XY: 0.0279 AC XY: 2078 AN XY: 74456

African (AFR) AF: 0.00705 AC: 293 AN: 41548

American (AMR) AF: 0.0241 AC: 368 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.0133 AC: 64 AN: 4824

European-Finnish (FIN) AF: 0.0605 AC: 642 AN: 10610

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0389 AC: 2648 AN: 68028

Other (OTH) AF: 0.0236 AC: 50 AN: 2116

Alfa AF: 0.0242 Hom.: 16

Bravo AF: 0.0237

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

ClinVar submissions

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	-0.47
CADD	Benign	7.6
DANN	Benign	0.78
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism

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: rs72804764; hg19: chr16-83828916;