rs1048612

Variant names:

• chr16-83783414-A-G
• rs1048612
• NM_001257.5:c.2076A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-83783414-A-G
• chr16-83783414-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001257.5(CDH13):​c.2076A>G​(p.Ala692Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,613,744 control chromosomes in the GnomAD database, including 526,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (50344 hom., cov: 32)
  • Exomes 𝑓: 0.81 (475825 hom.)
• Consequence: CDH13 NM_001257.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.86
• Publications: 17 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]

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-83783414-A-G is Benign according to our data. Variant chr16-83783414-A-G is described in ClinVar as Benign. ClinVar VariationId is 257647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.86 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.2076A>G	p.Ala692Ala	synonymous_variant	Exon 13 of 14	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.2076A>G	p.Ala692Ala	synonymous_variant	Exon 13 of 14	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123619 AN: 152044 Hom.: 50309 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.823

GnomAD2 exomes AF: 0.811 AC: 202165 AN: 249184 AF XY: 0.810

Gnomad AFR exome AF: 0.835

Gnomad AMR exome AF: 0.851

Gnomad ASJ exome AF: 0.785

Gnomad EAS exome AF: 0.797

Gnomad FIN exome AF: 0.804

Gnomad NFE exome AF: 0.803

Gnomad OTH exome AF: 0.809

GnomAD4 exome AF: 0.807 AC: 1178904 AN: 1461582 Hom.: 475825 Cov.: 58 AF XY: 0.806 AC XY: 586364 AN XY: 727084

African (AFR) AF: 0.835 AC: 27942 AN: 33476

American (AMR) AF: 0.851 AC: 38054 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 20485 AN: 26136

East Asian (EAS) AF: 0.801 AC: 31779 AN: 39698

South Asian (SAS) AF: 0.812 AC: 69999 AN: 86254

European-Finnish (FIN) AF: 0.806 AC: 43045 AN: 53396

Middle Eastern (MID) AF: 0.830 AC: 4786 AN: 5766

European-Non Finnish (NFE) AF: 0.805 AC: 894441 AN: 1111762

Other (OTH) AF: 0.801 AC: 48373 AN: 60370

GnomAD4 genome AF: 0.813 AC: 123707 AN: 152162 Hom.: 50344 Cov.: 32 AF XY: 0.813 AC XY: 60455 AN XY: 74384

African (AFR) AF: 0.832 AC: 34526 AN: 41502

American (AMR) AF: 0.841 AC: 12868 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2708 AN: 3472

East Asian (EAS) AF: 0.789 AC: 4069 AN: 5160

South Asian (SAS) AF: 0.813 AC: 3920 AN: 4820

European-Finnish (FIN) AF: 0.803 AC: 8505 AN: 10598

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54465 AN: 67994

Other (OTH) AF: 0.816 AC: 1726 AN: 2114

Alfa AF: 0.808 Hom.: 178480

Bravo AF: 0.819

Asia WGS AF: 0.803 AC: 2793 AN: 3478

EpiCase AF: 0.808

EpiControl AF: 0.806

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.045
DANN	Benign	0.29
PhyloP100		-1.9
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: rs1048612; hg19: chr16-83817019; COSMIC: COSV51841205;